Theoretical Studies of Interactions between O-Phosphorylated and Standard Amino-Acid Side-Chain Models in Water

PubMed Central

Wiśniewska, Marta; Sobolewski, Emil; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.; Makowski, Mariusz

2015-01-01

Phosphorylation is a common post-translational modification of the amino-acid side chains (serine, tyrosine, and threonine) that contain hydroxyl groups. The transfer of the negatively charged phosphate group from an ATP molecule to such amino-acid side chains leads to changes in the local conformations of proteins and the pattern of interactions with other amino-acid side-chains. A convenient characteristic of the side chain–side chain interactions in the context of an aqueous environment is the potential of mean force (PMF) in water. A series of umbrella-sampling molecular dynamic (MD) simulations with the AMBER force field were carried out for pairs of O-phosphorylated serine (pSer), threonine (pThr), and tyrosine, (pTyr) with natural amino acids in a TIP3P water model as a solvent at 298 K. The weighted-histogram analysis method was used to calculate the four-dimensional potentials of mean force. The results demonstrate that the positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the relative orientation depend on the character of the interacting pairs. More distinct minima are observed for oppositely charged pairs such as, e.g., O-phosphorylated side-chains and positively charged ones, such as the side-chains of lysine and arginine. PMID:26100791

Role of Side-Chain Molecular Features in Tuning Lower Critical Solution Temperatures (LCSTs) of Oligoethylene Glycol Modified Polypeptides.

PubMed

Gharakhanian, Eric G; Deming, Timothy J

2016-07-07

A series of thermoresponsive polypeptides has been synthesized using a methodology that allowed facile adjustment of side-chain functional groups. The lower critical solution temperature (LCST) properties of these polymers in water were then evaluated relative to systematic molecular modifications in their side-chains. It was found that in addition to the number of ethylene glycol repeats in the side-chains, terminal and linker groups also have substantial and predictable effects on cloud point temperatures (Tcp). In particular, we found that the structure of these polypeptides allowed for inclusion of polar hydroxyl groups, which significantly increased their hydrophilicity and decreased the need to use long oligoethylene glycol repeats to obtain LCSTs. The thioether linkages in these polypeptides were found to provide an additional structural feature for reversible switching of both polypeptide conformation and thermoresponsive properties.

Conditional Solvation Thermodynamics of Isoleucine in Model Peptides and the Limitations of the Group-Transfer Model

PubMed Central

2015-01-01

The hydration thermodynamics of the amino acid X relative to the reference G (glycine) or the hydration thermodynamics of a small-molecule analog of the side chain of X is often used to model the contribution of X to protein stability and solution thermodynamics. We consider the reasons for successes and limitations of this approach by calculating and comparing the conditional excess free energy, enthalpy, and entropy of hydration of the isoleucine side chain in zwitterionic isoleucine, in extended penta-peptides, and in helical deca-peptides. Butane in gauche conformation serves as a small-molecule analog for the isoleucine side chain. Parsing the hydrophobic and hydrophilic contributions to hydration for the side chain shows that both of these aspects of hydration are context-sensitive. Furthermore, analyzing the solute–solvent interaction contribution to the conditional excess enthalpy of the side chain shows that what is nominally considered a property of the side chain includes entirely nonobvious contributions of the background. The context-sensitivity of hydrophobic and hydrophilic hydration and the conflation of background contributions with energetics attributed to the side chain limit the ability of a single scaling factor, such as the fractional solvent exposure of the group in the protein, to map the component energetic contributions of the model-compound data to their value in the protein. But ignoring the origin of cancellations in the underlying components the group-transfer model may appear to provide a reasonable estimate of the free energy for a given error tolerance. PMID:24650057

Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

PubMed Central

Hyslop, Newton E.; Milligan, Richard J.

1974-01-01

The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (KD and KAV) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO4), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry. PMID:15825415

THE RELATION OF CHEMICAL STRUCTURE IN CATECHOL COMPOUNDS AND DERIVATIVES TO POISON IVY HYPERSENSITIVENESS IN MAN AS SHOWN BY THE PATCH TEST

PubMed Central

Keil, Harry; Wasserman, David; Dawson, Charles R.

1944-01-01

1. Additional evidence is presented in support of the view which postulates a close chemical and biologic relation between the active ingredients in poison ivy and Japan lac. 2. Biologic evidence, based on the use of the patch test in man, is presented in support of the view that the active ingredient in poison ivy is a catechol derivative with a long, unsaturated side-chain in the 3-position. 3. Of the catechol compounds and derivatives studied, group reactions in patients sensitive to poison ivy leaves or extract were exhibited by the following compounds: 3-pentadecyl catechol (100 per cent of 21 cases), 4-pentadecyl catechol (38 per cent of 21 cases), "urushiol" dimethyl ether (33 per cent of 33 cases), 3-pentadecenyl-1'-veratrole (21 per cent of 14 cases), 3-methyl catechol (14 per cent of 21 cases), and hydrourushiol dimethyl ether (10 per cent of 20 cases). It has been found that 3-geranyl catechol shows a practically constant group reactivity in persons sensitive to poison ivy. 4. The uniformly positive group reaction to 3-pentadecyl catechol is notable since this substance possesses a saturated side-chain, whereas the active ingredient in poison ivy is known to have an unsaturated side-chain. 5. The group reactivity was not restricted to the 3-position, for in some instances 4-pentadecyl catechol also gave group reactions which, however, were less intense and less frequent than those shown by 3-pentadecyl catechol. This indicates that in some cases a long side-chain in the 4 position may be effective in producing group specific reactions. 6. Only an occasional person showed sensitiveness to 3-methyl catechol (short side-chain), and in one instance the group reactivity appeared to be specific for the 3-position. 7. The position of the side-chain in the catechol configuration has some bearing on the degree and incidence of group reactions in persons hypersensitive to poison ivy. 8. Evidence is presented to indicate that the introduction of double bonds in the alkyl side-chain increases the incidence and intensity of group reactions. 9. Methylating the hydroxyl groups in the catechol configuration diminishes strongly the incidence of group reactivity but does not eliminate it entirely in persons hypersensitive to poison ivy. Thus, "urushiol" dimethyl ether (3-pentadecadienyl veratrole) gave group reactions in 33 per cent of 33 persons. 10. Methylating the hydroxyl groups as well as saturating the double bonds in the alkyl side-chain still further diminishes the group reactions but an occasional person hypersensitive to poison ivy may still show positive reaction to such a substance as 3-pentadecyl veratrole (hydrourushiol dimethyl ether). In this respect our results are not in full agreement with those recorded by Toyama who stated that hydrourushiol dimethyl ether is entirely harmless. 11. The significance of the group reactivity displayed by certain veratrole compounds is discussed, and several possible explanations of their behavior are advanced. 12. The group reactions discussed in this paper relate only to various catechol and veratrole compounds. Preliminary studies by us indicate that this sensitiveness extends to other phenolic derivatives. 13. Among the veratrole compounds showing positive reactions, the order of frequency and intensity was: (1) "urushiol" dimethyl ether (average of two double bonds); (2) S-pentadecenyl-1'-veratrole (one double bond); (3) hydrourushiol dimethyl ether (saturated side-chain). It may be noted that 4-pentadecyl veratrole was inactive. PMID:19871415

THE RELATION OF CHEMICAL STRUCTURE IN CATECHOL COMPOUNDS AND DERIVATIVES TO POISON IVY HYPERSENSITIVENESS IN MAN AS SHOWN BY THE PATCH TEST.

PubMed

Keil, H; Wasserman, D; Dawson, C R

1944-10-01

1. Additional evidence is presented in support of the view which postulates a close chemical and biologic relation between the active ingredients in poison ivy and Japan lac. 2. Biologic evidence, based on the use of the patch test in man, is presented in support of the view that the active ingredient in poison ivy is a catechol derivative with a long, unsaturated side-chain in the 3-position. 3. Of the catechol compounds and derivatives studied, group reactions in patients sensitive to poison ivy leaves or extract were exhibited by the following compounds: 3-pentadecyl catechol (100 per cent of 21 cases), 4-pentadecyl catechol (38 per cent of 21 cases), "urushiol" dimethyl ether (33 per cent of 33 cases), 3-pentadecenyl-1'-veratrole (21 per cent of 14 cases), 3-methyl catechol (14 per cent of 21 cases), and hydrourushiol dimethyl ether (10 per cent of 20 cases). It has been found that 3-geranyl catechol shows a practically constant group reactivity in persons sensitive to poison ivy. 4. The uniformly positive group reaction to 3-pentadecyl catechol is notable since this substance possesses a saturated side-chain, whereas the active ingredient in poison ivy is known to have an unsaturated side-chain. 5. The group reactivity was not restricted to the 3-position, for in some instances 4-pentadecyl catechol also gave group reactions which, however, were less intense and less frequent than those shown by 3-pentadecyl catechol. This indicates that in some cases a long side-chain in the 4 position may be effective in producing group specific reactions. 6. Only an occasional person showed sensitiveness to 3-methyl catechol (short side-chain), and in one instance the group reactivity appeared to be specific for the 3-position. 7. The position of the side-chain in the catechol configuration has some bearing on the degree and incidence of group reactions in persons hypersensitive to poison ivy. 8. Evidence is presented to indicate that the introduction of double bonds in the alkyl side-chain increases the incidence and intensity of group reactions. 9. Methylating the hydroxyl groups in the catechol configuration diminishes strongly the incidence of group reactivity but does not eliminate it entirely in persons hypersensitive to poison ivy. Thus, "urushiol" dimethyl ether (3-pentadecadienyl veratrole) gave group reactions in 33 per cent of 33 persons. 10. Methylating the hydroxyl groups as well as saturating the double bonds in the alkyl side-chain still further diminishes the group reactions but an occasional person hypersensitive to poison ivy may still show positive reaction to such a substance as 3-pentadecyl veratrole (hydrourushiol dimethyl ether). In this respect our results are not in full agreement with those recorded by Toyama who stated that hydrourushiol dimethyl ether is entirely harmless. 11. The significance of the group reactivity displayed by certain veratrole compounds is discussed, and several possible explanations of their behavior are advanced. 12. The group reactions discussed in this paper relate only to various catechol and veratrole compounds. Preliminary studies by us indicate that this sensitiveness extends to other phenolic derivatives. 13. Among the veratrole compounds showing positive reactions, the order of frequency and intensity was: (1) "urushiol" dimethyl ether (average of two double bonds); (2) S-pentadecenyl-1'-veratrole (one double bond); (3) hydrourushiol dimethyl ether (saturated side-chain). It may be noted that 4-pentadecyl veratrole was inactive.

Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR.

PubMed

Gerecht, Karola; Figueiredo, Angelo Miguel; Hansen, D Flemming

2017-09-16

Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the N ε -C ζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised.

Conformational analysis investigation into the influence of nano-porosity of ultra-permeable ultra-selective polyimides on its diffusivity as potential membranes for use in the "green" separation of natural gases

NASA Astrophysics Data System (ADS)

Madkour, Tarek M.

2013-08-01

Nano-porous polymers of intrinsic microporosity, PIM, have exhibited excellent permeability and selectivity characteristics that could be utilized in an environmentally friendly gas separation process. A full understanding of the mechanism through which these membranes effectively and selectively allow for the permeation of specific gases will lead to further development of these membranes. Three factors obviously influenced the conformational behavior of these polymers, which are the presence of electronegative atoms, the presence of non-linearity in the polymeric backbones (backbone kinks) and the presence of bulky side groups on the polymeric chains. The dipole moment increased sharply with the presence of backbone kinks more than any other factor. Replacing the fluorine atoms with bulky alkyl groups didn't influence the dipole moment greatly indicating that the size of the side chains had much less dramatic influence on the dipole moment than having a bent backbone. Similarly, the presence of the backbone kinks in the polymeric chains influenced the polymeric chains to assume less extended configuration causing the torsional angles around the interconnecting bonds unable to cross the high potential energy barriers. The presence of the bulky side groups also caused the energy barriers of the cis-configurations to increase dramatically, which prevented the polymeric segments from experiencing full rotation about the connecting bonds. For these polymers, it was clear that the fully extended configurations are the preferred configurations in the absence of strong electronegative atoms, backbones kinks or bulky side groups. The addition of any of these factors to the polymeric structures resulted in the polymeric chains being forced to assume less extended configurations. Rather interestingly, the length or bulkiness of the side groups didn't affect the end-to-end distance distribution to a great deal since the presence of quite large bulky side chain such as the pentyl group has caused the polymeric chains to revert back to the fully extended configurations possibly due to the quite high potential energy barriers that the chains have to cross to reach the less extended configurational states.

Frequent side chain methyl carbon-oxygen hydrogen bonding in proteins revealed by computational and stereochemical analysis of neutron structures.

PubMed

Yesselman, Joseph D; Horowitz, Scott; Brooks, Charles L; Trievel, Raymond C

2015-03-01

The propensity of backbone Cα atoms to engage in carbon-oxygen (CH · · · O) hydrogen bonding is well-appreciated in protein structure, but side chain CH · · · O hydrogen bonding remains largely uncharacterized. The extent to which side chain methyl groups in proteins participate in CH · · · O hydrogen bonding is examined through a survey of neutron crystal structures, quantum chemistry calculations, and molecular dynamics simulations. Using these approaches, methyl groups were observed to form stabilizing CH · · · O hydrogen bonds within protein structure that are maintained through protein dynamics and participate in correlated motion. Collectively, these findings illustrate that side chain methyl CH · · · O hydrogen bonding contributes to the energetics of protein structure and folding. © 2014 Wiley Periodicals, Inc.

Crystallization of dienelactone hydrolase in two space groups: structural changes caused by crystal packing

PubMed Central

Porter, Joanne L.; Carr, Paul D.; Collyer, Charles A.; Ollis, David L.

2014-01-01

Dienelactone hydrolase (DLH) is a monomeric protein with a simple α/β-hydrolase fold structure. It readily crystallizes in space group P212121 from either a phosphate or ammonium sulfate precipitation buffer. Here, the structure of DLH at 1.85 Å resolution crystallized in space group C2 with two molecules in the asymmetric unit is reported. When crystallized in space group P212121 DLH has either phosphates or sulfates bound to the protein in crucial locations, one of which is located in the active site, preventing substrate/inhibitor binding. Another is located on the surface of the enzyme coordinated by side chains from two different molecules. Crystallization in space group C2 from a sodium citrate buffer results in new crystallographic protein–protein interfaces. The protein backbone is highly similar, but new crystal contacts cause changes in side-chain orientations and in loop positioning. In regions not involved in crystal contacts, there is little change in backbone or side-chain configuration. The flexibility of surface loops and the adaptability of side chains are important factors enabling DLH to adapt and form different crystal lattices. PMID:25005082

Synthesis of diketopyrrolopyrrole-based polymers with polydimethylsiloxane side chains and their application in organic field-effect transistors

NASA Astrophysics Data System (ADS)

Ohnishi, Inori; Hashimoto, Kazuhito; Tajima, Keisuke

2018-03-01

Linear polydimethylsiloxane (PDMS) was investigated as a solubilizing group for π-conjugated polymers with the aim of combining high solubility in organic solvents with the molecular packing in solid films that is advantageous for charge transport. Diketopyrrolopyrrole-based copolymers with different contents and substitution patterns of the PDMS side chains were synthesized and evaluated for application in organic field-effect transistors. The PDMS side chains greatly increased the solubility of the polymers and led to shorter d-spacings of the π-stacking in the thin films compared with polymers containing conventional branched alkyl side chains.

SIRIUS. An automated method for the analysis of the preferred packing arrangements between protein groups.

PubMed

Singh, J; Thornton, J M

1990-02-05

Automated methods have been developed to determine the preferred packing arrangement between interacting protein groups. A suite of FORTRAN programs, SIRIUS, is described for calculating and analysing the geometries of interacting protein groups using crystallographically derived atomic co-ordinates. The programs involved in calculating the geometries search for interacting pairs of protein groups using a distance criterion, and then calculate the spatial disposition and orientation of the pair. The second set of programs is devoted to analysis. This involves calculating the observed and expected distributions of the angles and assessing the statistical significance of the difference between the two. A database of the geometries of the 400 combinations of side-chain to side-chain interaction has been created. The approach used in analysing the geometrical information is illustrated here with specific examples of interactions between side-chains, peptide groups and particular types of atom. At the side-chain level, an analysis of aromatic-amino interactions, and the interactions of peptide carbonyl groups with arginine residues is presented. At the atomic level the analyses include the spatial disposition of oxygen atoms around tyrosine residues, and the frequency and type of contact between carbon, nitrogen and oxygen atoms. This information is currently being applied to the modelling of protein interactions.

Modulation of p-Cyanophenylalanine Fluorescence by Amino Acid Side-chains and Rational Design of Fluorescence Probes of α-Helix Formation

PubMed Central

Taskent-Sezgin, Humeyra; Marek, Peter; Thomas, Rosanne; Goldberg, Daniel; Chung, Juah; Carrico, Isaac; Raleigh, Daniel P.

2011-01-01

p-Cyanophenylalanine is an extremely useful fluorescence probe of protein structure which can be recombinantly and chemically incorporated into proteins. The probe has been used to study protein folding, protein-membrane interactions, protein-peptide interactions and amyloid formation, however the factors that control its fluorescence are not fully understood. Hydrogen bonding to the cyano group is known to play a major role in modulating the fluorescence quantum yield, but the role of potential side-chain quenchers has not yet been elucidated. A systematic study on the effects of different side-chains on p-cyanophenylalanine fluorescence is reported. Tyr is found to have the largest effect followed by deprotonated His, Met, Cys, protonated His, Asn, Arg, and protonated Lys. Deprotonated amino groups are much more effective fluorescence quenchers than protonated amino groups. Free neutral imidazole and hydroxide ion are also effective quenchers of p-cyanophenylalanine fluorescence with Stern-Volmer constants of 39.8 M−1 and 22.1 M−1, respectively. The quenching of p-cyanophenylalanine fluorescence by specific side-chains is exploited to develop specific, high sensitivity, fluorescence probes of helix formation. The approach is demonstrated with Ala based peptides that contain a p-cyanophenylalanine-His or a p-cyanophenylalanine-Tyr pair located at positions i and i+4. The p-cyanophenylalanine-His pair is most useful when the His side-chain is deprotonated and is, thus, complimentary to Trp-His pair which is most sensitive when the His side-chain is protonated. PMID:20565125

Binding cooperativity between a ligand carbonyl group and a hydrophobic side chain can be enhanced by additional H-bonds in a distance dependent manner: A case study with thrombin inhibitors.

PubMed

Said, Ahmed M; Hangauer, David G

2015-01-01

One of the underappreciated non-covalent binding factors, which can significantly affect ligand-protein binding affinity, is the cooperativity between ligand functional groups. Using four different series of thrombin inhibitors, we reveal a strong positive cooperativity between an H-bond accepting carbonyl functionality and the adjacent P3 hydrophobic side chain. Adding an H-bond donating amine adjacent to the P3 hydrophobic side chain further increases this positive cooperativity thereby improving the Ki by as much as 546-fold. In contrast, adding an amidine multiple H-bond/salt bridge group in the distal S1 pocket does not affect this cooperativity. An analysis of the crystallographic B-factors of the ligand groups inside the binding site indicates that the strong cooperativity is mainly due to a significant mutual reduction in the residual mobility of the hydrophobic side chain and the H-bonding functionalities that is absent when the separation distance is large. This type of cooperativity is important to encode in binding affinity prediction software, and to consider in SAR studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Bis(thienothiophenyl) diketopyrrolopyrrole-based conjugated polymers with various branched alkyl side chains and their applications in thin-film transistors and polymer solar cells.

PubMed

Shin, Jicheol; Park, Gi Eun; Lee, Dae Hee; Um, Hyun Ah; Lee, Tae Wan; Cho, Min Ju; Choi, Dong Hoon

2015-02-11

New thienothiophene-flanked diketopyrrolopyrrole and thiophene-containing π-extended conjugated polymers with various branched alkyl side-chains were successfully synthesized. 2-Octyldodecyl, 2-decyltetradecyl, 2-tetradecylhexadecyl, 2-hexadecyloctadecyl, and 2-octadecyldocosyl groups were selected as the side-chain moieties and were anchored to the N-positions of the thienothiophene-flanked diketopyrrolopyrrole unit. All five polymers were found to be soluble owing to the bulkiness of the side chains. The thin-film transistor based on the 2-tetradecylhexadecyl-substituted polymer showed the highest hole mobility of 1.92 cm2 V(-1) s(-1) due to it having the smallest π-π stacking distance between the polymer chains, which was determined by grazing incidence X-ray diffraction. Bulk heterojunction polymer solar cells incorporating [6,6]-phenyl-C71-butyric acid methyl ester as the n-type molecule and the additive 1,8-diiodooctane (1 vol %) were also constructed from the synthesized polymers without thermal annealing; the device containing the 2-octyldodecyl-substituted polymer exhibited the highest power conversion efficiency of 5.8%. Although all the polymers showed similar physical properties, their device performance was clearly influenced by the sizes of the branched alkyl side-chain groups.

Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc04821a

PubMed Central

Gerecht, Karola; Figueiredo, Angelo Miguel

2017-01-01

Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the Nε–Cζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised. PMID:28840203

Side-chain to backbone interactions dictate the conformational preferences of a cyclopentane arginine analogue

PubMed Central

Revilla-López, Guillem; Torras, Juan; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos

2009-01-01

The intrinsic conformational preferences of the non-proteinogenic amino acids constructed by incorporating the arginine side chain in the β position of 1-aminocyclopentane-1-carboxylic acid (either in a cis or a trans orientation relative to the amino group) have been investigated using computational methods. These compounds may be considered as constrained analogues of arginine (denoted as c5Arg) in which the orientation of the side chain is fixed by the cyclopentane moiety. Specifically, the N-acetyl-N′-methylamide derivatives of cis and trans-c5Arg have been examined in the gas phase and in solution using B3LYP/6-311+G(d,p) calculations and Molecular Dynamics simulations. Results indicate that the conformational space available to these compounds is highly restricted, their conformational preferences being dictated by the ability of the guanidinium group in the side chain to establish hydrogen-bond interactions with the backbone. A comparison with the behavior previously described for the analogous phenylalanine derivatives is presented. PMID:19236034

Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.

PubMed

Hoernke, Maria; Schwieger, Christian; Kerth, Andreas; Blume, Alfred

2012-07-01

Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.

Coulomb repulsion in short polypeptides.

PubMed

Norouzy, Amir; Assaf, Khaleel I; Zhang, Shuai; Jacob, Maik H; Nau, Werner M

2015-01-08

Coulomb repulsion between like-charged side chains is presently viewed as a major force that impacts the biological activity of intrinsically disordered polypeptides (IDPs) by determining their spatial dimensions. We investigated short synthetic models of IDPs, purely composed of ionizable amino acid residues and therefore expected to display an extreme structural and dynamic response to pH variation. Two synergistic, custom-made, time-resolved fluorescence methods were applied in tandem to study the structure and dynamics of the acidic and basic hexapeptides Asp6, Glu6, Arg6, Lys6, and His6 between pH 1 and 12. (i) End-to-end distances were obtained from the short-distance Förster resonance energy transfer (sdFRET) from N-terminal 5-fluoro-l-tryptophan (FTrp) to C-terminal Dbo. (ii) End-to-end collision rates were obtained for the same peptides from the collision-induced fluorescence quenching (CIFQ) of Dbo by FTrp. Unexpectedly, the very high increase of charge density at elevated pH had no dynamical or conformational consequence in the anionic chains, neither in the absence nor in the presence of salt, in conflict with the common view and in partial conflict with accompanying molecular dynamics simulations. In contrast, the cationic peptides responded to ionization but with surprising patterns that mirrored the rich individual characteristics of each side chain type. The contrasting results had to be interpreted, by considering salt screening experiments, N-terminal acetylation, and simulations, in terms of an interplay of local dielectric constant and peptide-length dependent side chain charge-charge repulsion, side chain functional group solvation, N-terminal and side chain charge-charge repulsion, and side chain-side chain as well as side chain-backbone interactions. The common picture that emerged is that Coulomb repulsion between water-solvated side chains is efficiently quenched in short peptides as long as side chains are not in direct contact with each other or the main chain.

[Study on anti-bacterium activity of ginkgolic acids and their momomers].

PubMed

Yang, Xiaoming; Zhu, Wei; Chen, Jun; Qian, Zhiyu; Xie, Jimin

2004-09-01

Ginkgolic acids and their three monomers were separated from ginkgo sarcotestas. The anti-bacterium activity of ginkgolic acids were tested. The relation between the anti-bacterium activity and side chain of ginkgolic acid were studied. The MIC of ginkgolic acids and their three monomers and salicylic acid were tested. Ginkgolic acid has strong inhibitive effect on G+-bacterium. Salicylic acid has no side chain, so no anti-bacterial activity. When the length of gingkolic acid side chain is C13:0, it has the strongest anti-bacterial activity in three monomers. The side chain of ginkgolic acid is the key functional group that possessed anti-bacterial activity. The length of Ginkgolic acid was the main effective factor of anti-bacterial activity.

Highly conductive side chain block copolymer anion exchange membranes.

PubMed

Wang, Lizhu; Hickner, Michael A

2016-06-28

Block copolymers based on poly(styrene) having pendent trimethyl styrenylbutyl ammonium (with four carbon ring-ionic group alkyl linkers) or benzyltrimethyl ammonium groups with a methylene bridge between the ring and ionic group were synthesized by reversible addition-fragmentation radical (RAFT) polymerization as anion exchange membranes (AEMs). The C4 side chain polymer showed a 17% increase in Cl(-) conductivity of 33.7 mS cm(-1) compared to the benzyltrimethyl ammonium sample (28.9 mS cm(-1)) under the same conditions (IEC = 3.20 meq. g(-1), hydration number, λ = ∼7.0, cast from DMF/1-propanol (v/v = 3 : 1), relative humidity = 95%). As confirmed by small angle X-ray scattering (SAXS), the side chain block copolymers with tethered ammonium cations showed well-defined lamellar morphologies and a significant reduction in interdomain spacing compared to benzyltrimethyl ammonium containing block copolymers. The chemical stabilities of the block copolymers were evaluated under severe, accelerated conditions, and degradation was observed by (1)H NMR. The block copolymer with C4 side chain trimethyl styrenylbutyl ammonium motifs displayed slightly improved stability compared to that of a benzyltrimethyl ammonium-based AEM at 80 °C in 1 M NaOD aqueous solution for 30 days.

Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C.

PubMed

Häckel, M; Hinz, H J; Hedwig, G R

1999-11-15

The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine, histidine, cysteine, proline, glutamic acid, and arginine, have been determined in aqueous solution over the temperature range 10-90 degrees C using differential scanning densitometry . These data, together with those reported previously, have been used to derive the partial molar volumes of the side-chains of all 20 amino acids. The side-chain volumes are critically compared with literature values derived using partial molar volumes for alternative model compounds. The new amino acid side-chain volumes, along with that for the backbone glycyl group, were used to calculate the partial specific volumes of several proteins in aqueous solution. The results obtained are compared with those observed experimentally. The new side-chain volumes have also been used to re-determine residue volume changes upon protein folding.

Synthetic Lectins: New Tools for Detection and Management of Prostate Cancer

DTIC Science & Technology

2015-09-01

were synthesized on Tentagel resin analogous to those previously described.2 The effectiveness of the coupling was assessed using MALDI-MS in the...protecting groups on the Dab side -chains (where boronic acids are attached). This appeared to be a significant portion of the product, composing up...evaluate our synthetic approach and tried different side -chain amine protecting groups on Dab including alloc and MTT. From these studies, we

NMR and X-ray studies of isomeric 22,23-dihydroxy stigmastanes

NASA Astrophysics Data System (ADS)

Khripach, Vladimir A.; Zhabinskii, Vladimir N.; Ivanova, Galina V.; Fando, Galina P.; Tsavlovskii, Dmitrii V.; Khripach, Natalya B.; Lyakhov, Alexander S.; Misharin, Alexander Yu.

2010-06-01

A comparative conformational study of steroidal side chain of (22 R,23 R)- and (22 S,23 S)-dihydroxy stigmastane derivatives was performed using single crystal X-ray diffraction and NMR spectroscopy. The preferred conformation in solution was shown to be close to that in the crystal. (22 R,23 R)-Isomers typical for natural plant steroid hormones brassinosteroids adopt a conformation in which both hydroxyl groups are pointed toward unhindered α-side of the steroidal plane and can thus participate in biochemical processes. Unnatural (22 S,23 S)-counterparts exhibit a conformation with the two hydroxyl groups oriented in the opposite direction and sterically hindered by 21-methyl group and terminal side chain fragment.

Electron detachment of the hydrogen-bonded amino acid side-chain guanine complexes

NASA Astrophysics Data System (ADS)

Wang, Jing; Gu, Jiande; Leszczynski, Jerzy

2007-07-01

The photoelectron spectra of the hydrogen-bonded amino acid side-chain-guanine complexes has been studied at the partial third order (P3) self-energy approximation of the electron propagator theory. The correlation between the vertical electron detachment energy and the charge distributions on the guanine moiety reveals that the vertical electron detachment energy (VDE) increases as the positive charge distribution on the guanine increases. The low VDE values determined for the negatively charged complexes of the guanine-side-chain-group of Asp/Glu suggest that the influence of the H-bonded anionic groups on the VDE of guanine could be more important than that of the anionic backbone structure. The even lower vertical electron detachment energy for guanine is thus can be expected in the H-bonded protein-DNA systems.

Gemini analogs of vitamin D.

PubMed

Pazos, Gonzalo; Rivadulla, Marcos L; Pérez-García, Xenxo; Gandara, Zoila; Pérez, Manuel

2014-01-01

The Gemini analogs are the last significant contribution to the family of vitamin D derivatives in medicine, for the treatment of cancer. The first Gemini analog was characterized by two symmetric side chains at C-20. Following numerous modifications, the most active analog bears a C-23-triple bond, C-26, 27- hexafluoro substituents on one side chain and a terminal trideuteromethylhydroxy group on the other side chain. This progression was possible due to improvements in the synthetic methods for the preparation of these derivatives, which allowed for increasing molecular complexity and complete diastereoselective control at C-20 and the substituted sidechains.

Surprising Impact of Remote Groups on the Folding-Unfolding and Dimer-Chain Equilibria of Bifunctionl H-Bonding Unimers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Rui; Cheng, Shuang; Baker, Erin Shammel

2016-01-28

Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules.

Conformation, structure and molecular solvation: a spectroscopic and computational study of 2-phenoxy ethanol and its singly and multiply hydrated clusters

NASA Astrophysics Data System (ADS)

Macleod, Neil A.; Simons, John P.

2002-10-01

The conformational landscapes of 2-phenoxy ethanol (POX) and its hydrated clusters have been studied in the gas-phase, providing a model for pharmaceutical β-blockers. A combination of experimental techniques, including resonant two-photon ionisation (R2PI), laser-induced-fluorescence (LIF) and resonant ion-dip infra-red spectroscopy (RIDIRS), coupled with high-level ab initio calculations has allowed the assignment of the individually resolved spectral features to discrete conformational and supra-molecular structures. Assignments were made by comparison of experimental vibrational spectra and partially resolved ultra-violet rotational band contours with those predicted from quantum chemical calculations. The isolated molecule displays a solitary structure with an extended geometry of the side-chain which is stabilised by an intramolecular hydrogen-bond between the alcohol (proton donor) and the ether (proton acceptor) groups of the side-chain. In singly hydrated clusters the water molecule is accommodated by insertion into the intramolecular hydrogen-bond. In the doubly hydrated and higher clusters cyclic structures are generated which incorporate both the water molecules and the terminal OH group of the side-chain; additional (weak) hydrogen bonded interactions with the phenoxy group provide a degree of selectivity but essentially, the water 'droplet' forms on the end of the alcohol side-chain.

Effect of methyl groups on conformational properties of small ionized comb-like polyelectrolytes at the atomic level.

PubMed

Zhao, Hongxia; Liu, Jiaping; Ran, Qianping; Yang, Yong; Shu, Xin

2017-03-01

Comb-like polycarboxylate ether (PCE) molecules with different content of methyl groups substituted on backbone and different location of methyl groups substituted on the side chains, respectively, were designed and were studied in explicit salt solutions by all-atom molecular dynamics simulations. Methyl groups substituted on the backbone of PCE have a great effect on the conformation of PCE. Stiffness of charged backbone was not only affected by the rotational freedom but also the electrostatic repulsion between the charged COO - groups. The interaction of counterions (Na + ) with COO - groups for PCE3 (with part of AA substituted by MAA on the backbone) was stronger and the screen effect was great, which decided the smaller size of PCE3. The interaction between water and COO - groups was strong regardless of the content of AA substituted by MAA on the backbone. The effect of methyl groups substituted on the different location of side chains on the conformation of PCE was less than that of methyl groups substituted on the backbone. The equilibrium sizes of the four PCE molecules with methyl groups substituted on the side chains were similar. Graphical Abstract Effect of methyl groups on conformational properties of small ionized comb-like polyelectrolytes at the atomic level.

Oxidation of Peptides by Methyl(trifluoromethyl)dioxirane: the Protecting Group Matters

PubMed Central

Rella, Maria Rosaria; Williard, Paul G.

2011-01-01

Representative Boc protected and acetyl protected peptide methyl esters bearing alkyl side chains undergo effective oxidation using methyl(trifluoromethyl)dioxirane (1b) under mild conditions. We observe a protecting group dependency in the chemoselectivity displayed by the dioxirane 1b. N-hydroxylation occurs in the case of the Boc protected peptides, side chain hydroxylation takes place in the case of acetyl protected peptides. Both are attractive transformations since they yield derivatized peptides that serve as valuable synthons. PMID:17221970

Hydrogen bonding between phosphate and amino acid side chains

NASA Astrophysics Data System (ADS)

Carmona, P.; Rodriguez, M. L.

1986-03-01

Hydrogen bonds between polar groups of amino acid side chains (histidine, lysine, glutamic acid) and phosphate ions have been studied by infrared spectroscopy. Proton transfer from amino acid groups to phosphate occur mainly in case that tribasic and dibasic phosphate ions take part in hydrogen bonds. Conformational changes and continuum are strongly related to the degree of proton transfer and hydration. It is pointed out that the aforementioned properties should be of great significance for nucleation and growth of prostatic and renal stones.

Alternative Fluoropolymers to Avoid the Challenges Associated with Perfluorooctanoic Acid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo,J.; Resnick, P.; Efimenko, K.

2008-01-01

The degradation of stain-resistant coating materials leads to the release of biopersistent perfluorooctanoic acid (PFOA) to the environment. In order to find the environmentally friendly substitutes, we have designed and synthesized a series of nonbiopersistant fluorinated polymers containing perfluorobutyl groups in the side chains. The surface properties of the new coating materials were characterized by static and dynamic contact angle measurements. The new coating materials demonstrate promising hydrophobic and oleophobic properties with low surfaces tensions. The wetting properties and surface structure of the polymers were tuned by varying the 'spacer' structures between the polymer backbones and the perfluorinated groups ofmore » the side chains. The relationship between orientations of the fluorinated side chains and performances of polymer surfaces were further investigated by near-edge X-ray fine absorption structure (NEXAFS) experiments and differential scanning calorimetry (DSC).« less

Optical probe for the cytochrome P-450 cholesterol side chain cleavage enzyme

DOEpatents

Marrone, Babetta L.; Simpson, Daniel J.; Unkefer, Clifford J.; Whaley, Thomas W.

1992-01-01

An optical probe enables the study of enzyme activity by absorbance spectroscopy or by sensitive fluorescence methods. In particular, the probe provides the ability to monitor the activity of cytochrome P-450.sub.scc enzyme, the rate limiting enzyme for steroid biosynthesis. Located on the inner mitochondrial membrane, P-450.sub.scc catalyzes the conversion of cholesterol to pregnenolone and isocapraldehyde by sequential oxidations of the cholesterol side chain. The fluorogenic probe includes a cholesterol-like steroid linked to a chromophore through a linking group. The chromophore is selected to have little optical response when linked to the steroid substrate and an enhanced optical response when cleaved from the substrate and linking group. Thus, a fluorescent anion that can be optically detected is generated by the side-chain cleavage reaction during steroidogenesis.

Optical probe for the cytochrome P-450 cholesterol side chain cleavage enzyme

DOEpatents

Marrone, Babetta L.; Simpson, Daniel J.; Unkefer, Clifford J.; Whaley, Thomas W.

1993-01-01

An optical probe enables the study of enzyme activity by absorbance spectroscopy or by sensitive fluorescence methods. In particular, the probe provides the ability to monitor the activity of cytochrome P-450.sub.scc enzyme, the rate limiting enzyme for steroid biosynthesis. Located on the inner mitochondrial membrane, P-450.sub.scc catalyzes the conversion of cholesterol to pregnenolone and isocapraldehyde by sequential oxidations of the cholesterol side chain. The fluorogenic probe includes a cholesterol-like steroid linked to a chromophore through a linking group. The chromophore is selected to have little optical response when linked to the steroid substrate and an enhanced optical response when cleaved from the substrate and linking group. Thus, a fluorescent anion that can be optically detected is generated by the side-chain cleavage reaction during steroidogenesis.

Determination of the pKa of the N-terminal amino group of ubiquitin by NMR

PubMed Central

Oregioni, Alain; Stieglitz, Benjamin; Kelly, Geoffrey; Rittinger, Katrin; Frenkiel, Tom

2017-01-01

Ubiquitination regulates nearly every aspect of cellular life. It is catalysed by a cascade of three enzymes and results in the attachment of the C-terminal carboxylate of ubiquitin to a lysine side chain in the protein substrate. Chain extension occurs via addition of subsequent ubiquitin molecules to either one of the seven lysine residues of ubiquitin, or via its N-terminal α-amino group to build linear ubiquitin chains. The pKa of lysine side chains is around 10.5 and hence E3 ligases require a mechanism to deprotonate the amino group at physiological pH to produce an effective nucleophile. In contrast, the pKa of N-terminal α-amino groups of proteins can vary significantly, with reported values between 6.8 and 9.1, raising the possibility that linear chain synthesis may not require a general base. In this study we use NMR spectroscopy to determine the pKa for the N-terminal α-amino group of methionine1 of ubiquitin for the first time. We show that it is 9.14, one of the highest pKa values ever reported for this amino group, providing a rational for the observed need for a general base in the E3 ligase HOIP, which synthesizes linear ubiquitin chains. PMID:28252051

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.

PubMed

Kuo, Hsiou-Ting; Liu, Shing-Lung; Chiu, Wen-Chieh; Fang, Chun-Jen; Chang, Hsien-Chen; Wang, Wei-Ren; Yang, Po-An; Li, Jhe-Hao; Huang, Shing-Jong; Huang, Shou-Ling; Cheng, Richard P

2015-05-01

β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.

Abnormal viscoelastic behavior of side-chain liquid-crystal polymers

NASA Astrophysics Data System (ADS)

Gallani, J. L.; Hilliou, L.; Martinoty, P.; Keller, P.

1994-03-01

We show that, contrary to what is commonly believed, the isotropic phase of side-chain liquid-crystal polymers has viscoelastic properties which are totally different from those of ordinary flexible melt polymers. The results can be explained by the existence of a transient network created by the dynamic association of mesogenic groups belonging to different chains. The extremely high sensitivity of the compound to the state of the surfaces with which it is in contact offers us an unexpected method of studying surface states.

Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caselli, E.; Powers, R.A.; Blaszczak, L.C.

2010-03-05

Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well asmore » four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in {beta}-lactam inhibitors or {beta}-lactam substrates of serine {beta}-lactamases. Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities. The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series.« less

A molecular modeling approach to understand the structure and conformation relationship of (GlcpA)Xylan.

PubMed

Guo, Qingbin; Kang, Ji; Wu, Yan; Cui, Steve W; Hu, Xinzhong; Yada, Rickey Y

2015-12-10

The structure and conformation relationships of a heteropolysaccharide (GlcpA)Xylan in terms of various molecular weights, Xylp/GlcpA ratio and the distribution of GlcpA along xylan chain were investigated using computer modeling. The adiabatic contour maps of xylobiose, XylpXylp(GlcpA) and (GlcpA)XylpXylp(GlcpA) indicated that the insertion of the side group (GlcpA) influenced the accessible conformational space of xylobiose molecule. RIS-Metropolis Monte Carlo method indicated that insertion of GlcpA side chain induced a lowering effect of the calculated chain extension at low GlcpA:Xylp ratio (GlcpA:Xylp = 1:3). The chain, however, became extended when the ratio of GlcpA:Xylp above 2/3. It was also shown that the spatial extension of the polymer chains was dependent on the distribution of side chain: the random distribution demonstrated the most flexible structure compared to block and alternative distribution. The present studies provide a unique insight into the dependence of both side chain ratio and distribution on the stiffness and flexibility of various (GlcpA)Xylan molecules. Copyright © 2015. Published by Elsevier Ltd.

Synthesis of novel benzohydrazone-oxadiazole hybrids as β-glucuronidase inhibitors and molecular modeling studies.

PubMed

Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Selvaraj, Manikandan; Rahim, Abdul; Ali, Muhammad; Siddiqui, Salman; Rahim, Fazal; Khan, Khalid Mohammed

2015-12-01

A series of compounds consisting of 25 novel oxadiazole-benzohydrazone hybrids (6-30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6-30 were found to be in the range of 7.14-44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain's carboxamide NH (2.1Å). Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities.

PubMed

Sakane, Rie; Kimura, Kimito; Hirota, Yoshihisa; Ishizawa, Michiyasu; Takagi, Yuta; Wada, Akimori; Kuwahara, Shigefumi; Makishima, Makoto; Suhara, Yoshitomo

2017-11-01

Vitamin K is an essential cofactor of γ-glutamylcarboxylase as related to blood coagulation and bone formation. Menaquinone-4, one of the vitamin K homologues, is biosynthesized in the body and has various biological activities such as being a ligand for steroid and xenobiotic receptors, protection of neuronal cells from oxidative stress, and so on. From this background, we focused on the role of menaquinone in the differentiation activity of progenitor cells into neuronal cells and we synthesized novel vitamin K derivatives with modification of the ω-terminal side chain. We report here new vitamin K analogues, which introduced an alkylated phenyl group at the ω-terminal side chain. These compounds exhibited potent differentiation activity as compared to control. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Sum frequency generation and solid-state NMR study of the structure, orientation, and dynamics of polystyrene-adsorbed peptides

PubMed Central

Weidner, Tobias; Breen, Nicholas F.; Li, Kun; Drobny, Gary P.; Castner, David G.

2010-01-01

The power of combining sum frequency generation (SFG) vibrational spectroscopy and solid-state nuclear magnetic resonance (ssNMR) spectroscopy to quantify, with site specificity and atomic resolution, the orientation and dynamics of side chains in synthetic model peptides adsorbed onto polystyrene (PS) surfaces is demonstrated in this study. Although isotopic labeling has long been used in ssNMR studies to site-specifically probe the structure and dynamics of biomolecules, the potential of SFG to probe side chain orientation in isotopically labeled surface-adsorbed peptides and proteins remains largely unexplored. The 14 amino acid leucine-lysine peptide studied in this work is known to form an α-helical secondary structure at liquid-solid interfaces. Selective, individual deuteration of the isopropyl group in each leucine residue was used to probe the orientation and dynamics of each individual leucine side chain of LKα14 adsorbed onto PS. The selective isotopic labeling methods allowed SFG analysis to determine the orientations of individual side chains in adsorbed peptides. Side chain dynamics were obtained by fitting the deuterium ssNMR line shape to specific motional models. Through the combined use of SFG and ssNMR, the dynamic trends observed for individual side chains by ssNMR have been correlated with side chain orientation relative to the PS surface as determined by SFG. This combination provides a more complete and quantitative picture of the structure, orientation, and dynamics of these surface-adsorbed peptides than could be obtained if either technique were used separately. PMID:20628016

2D SMARTCyp Reactivity-Based Site of Metabolism Prediction for Major Drug-Metabolizing Cytochrome P450 Enzymes

DTIC Science & Technology

2012-05-25

3. (A) X-ray structure of human CYP2C9 cocrystallized with flurbiprofen showing hydrogen bonding interactions between the anionic carboxyl group with...Figure 3 shows the X-ray crystal structure of human CYP2C9 cocrystallized with flurbiprofen . The structure indicates that the carboxyl group of... flurbiprofen forms hydrogen bonding interactions with the Arg108 and Asn204 side chains of the protein.35 Since the Arg108 and Asn204 side chains are at the

ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction.

PubMed

Dhar, Jesmita; Chakrabarti, Pinak; Saini, Harpreet; Raghava, Gajendra Pal Singh; Kishore, Raghuvansh

2015-02-01

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼ three times per 100 residues. Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. © 2014 Wiley Periodicals, Inc.

Probing the effects of the ester functional group, alkyl side chain length and anions on the bulk nanostructure of ionic liquids: a computational study.

PubMed

Fakhraee, Mostafa; Gholami, Mohammad Reza

2016-04-14

The effects of ester addition on nanostructural properties of biodegradable ILs composed of 1-alkoxycarbonyl-3-alkyl-imidazolium cations ([C1COOCnC1im](+), n = 1, 2, 4) combined with [Br](-), [NO3](-), [BF4](-), [PF6](-), [TfO](-), and [Tf2N](-) were explored by using the molecular dynamics (MD) simulations and quantum theory of atoms in molecules (QTAIM) analysis at 400 K. Various thermodynamic properties of these ILs were extensively computed in our earlier work (Ind. Eng. Chem. Res., 2015, 54, 11678-11700). Nano-scale segregation analysis demonstrates the formation of a small spherical island-like hydrocarbon within the continuous ionic domain for ILs with short alkyl side chain ([C1COOC1C1im]), and a sponge-like nanostructure for the compound with long alkyl side chain ([C1COOC4C1im]). Ester-functionalized ILs with ethyl side chain ([C1COOC2C1im]) are the turning point between two different morphologies. Non-polar channels were observed for [C1COOC4C1im] ILs composed of smaller anions such as [Br] and [NO3], whereas clustering organization was found for the other anions. Formation of the spherical micelle-like nanostructure was seen for lengthened cations. Finally, the incorporation of an ester group into the alkyl side chain of the cation leads to stronger segregation between charged and uncharged networks, which consequently increased the possibility of self-assembly and micelle formation.

Erythrolic acids A-E, Meroterpenoids from a Marine-Derived Erythrobacter sp

PubMed Central

Hu, Youcai; Legako, Aaron G.; Espindola, Ana Paula D.M.; MacMillan, John B.

2012-01-01

Erythrolic acids A-E (1–5) are five unusual meroterpenoids isolated from the bacterium Erythrobacter sp. derived from a marine sediment sample collected in Galveston, TX. The structures were elucidated by means of detailed spectroscopic analysis and chemical derivatization. The erythrolic acids contain a 4-hydroxybenzoic acid appended with a modified terpene side chain. The side chain modifications include oxidation of a terminal methyl substituent and in the case of 1–4 addition of a 2-carbon unit to give terpene side chains of unusual length; C22 for 1 and 2, C17 for 3 and C12 for 4. The relative and absolute configurations of the meroterpenoids were determined by coupling constant, NOE and Mosher’s analysis. In vitro cytotoxicity towards a number of non-small cell lung cancer (NSCLC) cell lines revealed only modest activity for erythrolic acid D (4) (2.5 μM against HCC44). The discovery of these unusual diterpenes, along with the previously reported erythrazoles, demonstrate the natural product potential of a previously unstudied group of bacteria for drug discovery. The unusual nature of the terpene side chain, we believe, involves an oxidation of a terminal methyl group to a carboxylic acid and subsequent Claisen condensation with acetyl-CoA. PMID:22384985

4-N, 4-S & 4-O Chloroquine Analogues: Influence of Side Chain Length and Quinolyl Nitrogen pKa on Activity vs. Chloroquine Resistant Malaria+, #

PubMed Central

Natarajan, Jayakumar K.; Alumasa, John; Yearick, Kimberly; Ekoue-Kovi, Kekeli A.; Casabianca, Leah B.; de Dios, Angel C.; Wolf, Christian; Roepe, Paul D.

2009-01-01

Using predictions from heme – quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure – function principles. We vary side chain length for both monoethyl and diethyl 4N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position, and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4N, 4S and 4O derivatives vs. μ-oxo dimeric heme, measure binding constants for monomeric vs. dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs. CQR malaria. PMID:18512900

4-N-, 4-S-, and 4-O-chloroquine analogues: influence of side chain length and quinolyl nitrogen pKa on activity vs chloroquine resistant malaria.

PubMed

Natarajan, Jayakumar K; Alumasa, John N; Yearick, Kimberly; Ekoue-Kovi, Kekeli A; Casabianca, Leah B; de Dios, Angel C; Wolf, Christian; Roepe, Paul D

2008-06-26

Using predictions from heme-quinoline antimalarial complex structures, previous modifications of chloroquine (CQ), and hypotheses for chloroquine resistance (CQR), we synthesize and assay CQ analogues that test structure-function principles. We vary side chain length for both monoethyl and diethyl 4-N CQ derivatives. We alter the pKa of the quinolyl N by introducing alkylthio or alkoxy substituents into the 4 position and vary side chain length for these analogues. We introduce an additional titratable amino group to the side chain of 4-O analogues with promising CQR strain selectivity and increase activity while retaining selectivity. We solve atomic resolution structures for complexes formed between representative 4-N, 4-S, and 4-O derivatives vs mu-oxo dimeric heme, measure binding constants for monomeric vs dimeric heme, and quantify hemozoin (Hz) formation inhibition in vitro. The data provide additional insight for the design of CQ analogues with improved activity vs CQR malaria.

Origins of pressure-induced protein transitions.

PubMed

Chalikian, Tigran V; Macgregor, Robert B

2009-12-18

The molecular mechanisms underlying pressure-induced protein denaturation can be analyzed based on the pressure-dependent differences in the apparent volume occupied by amino acids inside the protein and when they are exposed to water in an unfolded conformation. We present here an analysis for the peptide group and the 20 naturally occurring amino acid side chains based on volumetric parameters for the amino acids in the interior of the native state, the micelle-like interior of the pressure-induced denatured state, and the unfolded conformation modeled by N-acetyl amino acid amides. The transfer of peptide groups from the protein interior to water becomes increasingly favorable as pressure increases. Thus, solvation of peptide groups represents a major driving force in pressure-induced protein denaturation. Polar side chains do not appear to exhibit significant pressure-dependent changes in their preference for the protein interior or solvent. The transfer of nonpolar side chains from the protein interior to water becomes more unfavorable as pressure increases. We conclude that a sizeable population of nonpolar side chains remains buried inside a solvent-inaccessible core of the pressure-induced denatured state. At elevated pressures, this core may become packed almost as tightly as the interior of the native state. The presence and partial disappearance of large intraglobular voids is another driving force facilitating pressure-induced denaturation of individual proteins. Our data also have implications for the kinetics of protein folding and shed light on the nature of the folding transition state ensemble.

Side-chain amino-acid-based pH-responsive self-assembled block copolymers for drug delivery and gene transfer.

PubMed

Kumar, Sonu; Acharya, Rituparna; Chatterji, Urmi; De, Priyadarsi

2013-12-10

Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

Synthesis of waterborne polyurethane containing alkoxysilane side groups and the properties of the hybrid coating films

NASA Astrophysics Data System (ADS)

Li, Qi; Guo, Longhai; Qiu, Teng; Xiao, Weidong; Du, Dianxing; Li, Xiaoyu

2016-07-01

A series of waterborne polyurethane (WPU) containing alkoxysilane side groups were synthesized by using the dihydroxy functionalized alkoxysilane. The diol with trimethoxysilane groups at the side chains was synthesized via Michael addition between 3-(methacryloxypropyl)trimethoxysilane (MAPTS) and diethanolamine (DEA). The silane diol was applied as the chain extender for the NCO-endcapped prepolymer of isophorone diisocyanate, polycarbonate diol, 2,2-bis(hydroxymethyl) butyric acid and 1,4-butanediol. The products with the silane content varied from 1.2 to 16.5 wt% were dispersed in water after neutralization. The effect of the silane diol on the particle size and morphology of the WPU dispersion was studied by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. X-ray photoelectron spectroscopy (XPS) characterization was carried out on the coating film of the WPU, revealing that the long flexible side chain is favorable for the silane components to emigrate toward the film surface and crosslink during the film formation process. As a result, both the surface contact angle to water and water adsorption of the WPU coating films increased with the silane content. Furthermore, the mechanical properties including the modulus and tensile strength of the films were also improved by the incorporation of silane diol.

Molecular Dynamics Simulation of Calbindin D9k in Apo, Singly and Doubly Loaded States in Various Side-Chains

NASA Astrophysics Data System (ADS)

Thapa, Mahendra Bahadur

Calbindin D9k (CAB) is a single domain calcium-binding protein and is the smallest members of the calmodulin superfamily, possessing a pair of calcium-binding EF-hands, and structures for all four states have been determined and extensively characterized experimentally. Because of the tremendous advancement in hardware and software computer technologies in recent years, longer and more realistic molecular dynamics (MD) simulations of a protein are possible now in reasonable periods of time. These advances were exploited to generate multiple, all-atom MD simulations of CAB via the AMBER software package, and the resulting trajectories were employed to calculate backbone order parameters of the apo, the singly and the doubly loaded states of calcium in CAB. The results are in very good agreement with corresponding experimental NMR-based (Nuclear Magnetic Resonance spectroscopy) results, and are improved in comparison to those calculated over a decade ago; use of modified force fields played a key role in the observed improvements. The apo state is the most flexible, and the singly loaded and the doubly loaded states are similar, thus supporting positive cooperativity in line with the experimental results. Further, B-factor calculations of backbone atoms for these calcium-binding states of calbindin D9k also support such cooperativity. Although changes in side-chain motions are not necessarily correlated to changes in protein backbone mobility, past studies on the comparison of experimental and simulated methyl side-chain NMR relaxation parameters of CAB for the doubly-loaded state reported significant improvements in the quantitative representation of side-chain motion by MD simulation. In this project, the order parameters for various side chains in apo, singly loaded and doubly loaded states of CAB were calculated. The primary goal of this work was to determine whether or not the allosteric effect of calcium binding, as observed via the backbone order parameters, also extended to the amino acid side chains, and if so, to what extent. Such information could be useful in better understanding the physical basis of cooperative calcium binding in CAB. Most of the residues which provide ligands to bind calcium at the binding sites support positive cooperativity, as observed when Ca-Cß, Cß-C?, C-C bond and C-O bonds of COO groups of aspartic and glutamic acid residues, the C-N bond of the side-chain amide group in asparagine and glutamine residues, and the N-H bonds of amide (NH2) group order parameters were studied. There are only a few residues containing methyl groups that are involved in providing ligands to the calcium, and the studies of order parameters of C-C bond and C-H bond of these methyl groups did not exhibit the cooperativity effect upon calcium binding; the simulated C-C bond order parameter of the methyl group symmetry axis did correlate well with the experimental results for the fully loaded state of CAB (4ICB). Analysis of the MD trajectories using GSATools and MutInf, provided valuable insights into possible pathways for communicating allosteric effects between the two calcium-binding sites of CAB.

An easy and effective method to modulate molecular energy level of the polymer based on benzodithiophene for the application in polymer solar cells.

PubMed

Zhang, Maojie; Guo, Xia; Ma, Wei; Zhang, Shaoqing; Huo, Lijun; Ade, Harald; Hou, Jianhui

2014-04-02

Attaching meta-alkoxy-phenyl groups as conjugated side chains is an easy and effective way to modulate the molecular energy level of D-A polymer for photovoltaic application, and the polymer solar cells based on the polymer consisting meta-alkoxy-phenyl groups as conjugated side chain, PBT-OP, shows an enhanced open circuit voltage and thus higher efficiency of 7.50%, under the illumination of AM 1.5G, 100 mW/cm(2) . © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular engineering of side-chain liquid crystalline polymers by living cationic polymerization using Webster`s initiating system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Percec, V.

1993-12-31

Webster`s cationic initiating system (HO{sub 3}SCF{sub 3}/SMe{sub 2}) (Macromolecules, 23, 1918 (1990)) was shown by us (for a review see Adv. Mater., 4, 548 (1992)) to polymerize, via a living mechanism, mesogenic vinyl ethers which contain a large variety of functional groups. This is mostly because SMe{sub 2} is a softer nucleophile than any of the functional groups available in these monomers. The molecular engineering of side-chain liquid crystalline polymers with conventional and complex architectures via this polymerization technique will be discussed.

A 13C{31P} REDOR NMR Investigation of the Role of Glutamic Acid Residues in Statherin-Hydroxyapatite Recognition

PubMed Central

Ndao, Moise; Ash, Jason T.; Breen, Nicholas F.; Goobes, Gil; Stayton, Patrick S.; Drobny, Gary P.

2011-01-01

The side chain carboxyl groups of acidic proteins found in the extra-cellular matrix (ECM) of mineralized tissues play a key role in promoting or inhibiting the growth of minerals such as hydroxyapatite (HAP), the principal mineral component of bone and teeth. Among the acidic proteins found in the saliva is statherin, a 43-residue tyrosine-rich peptide that is a potent lubricant in the salivary pellicle and an inhibitor of both HAP crystal nucleation and growth. Three acidic amino acids – D1, E4, and E5 – are located in the N-terminal 15 amino acid segment, with a fourth amino acid, E26, located outside the N-terminus. We have utilized 13C{31P} REDOR NMR to analyze the role played by acidic amino acids in the binding mechanism of statherin to the HAP surface by measuring the distance between the δ-carboxyl 13C spins of the three glutamic acid side chains of statherin (residues E4, E5, E26) and 31P spins of the phosphate groups at the HAP surface. 13C{31P} REDOR studies of glutamic-5-13C acid incorporated at positions E4 and E26 indicate a 13C–31P distance of more than 6.5 Å between the side chain carboxyl 13C spin of E4 and the closest 31P in the HAP surface. In contrast, the carboxyl 13C spin at E5 has a much shorter 13C–31P internuclear distance of 4.25±0.09 Å, indicating that the carboxyl group of this side chain interacts directly with the surface. 13C T1ρ and slow-spinning MAS studies indicate that the motions of the side chains of E4 and E5 are more restricted than that of E26. Together, these results provide further insight into the molecular interactions of statherin with HAP surfaces. PMID:19678690

Interaction of arginine, lysine, and guanidine with surface residues of lysozyme: implication to protein stability.

PubMed

Shah, Dhawal; Shaikh, Abdul Rajjak

2016-01-01

Additives are widely used to suppress aggregation of therapeutic proteins. However, the molecular mechanisms of effect of additives to stabilize proteins are still unclear. To understand this, we herein perform molecular dynamics simulations of lysozyme in the presence of three commonly used additives: arginine, lysine, and guanidine. These additives have different effects on stability of proteins and have different structures with some similarities; arginine and lysine have aliphatic side chain, while arginine has a guanidinium group. We analyze atomic contact frequencies to study the interactions of the additives with individual residues of lysozyme. Contact coefficient, quantified from contact frequencies, is helpful in analyzing the interactions with the guanidine groups as well as aliphatic side chains of arginine and lysine. Strong preference for contacts to the additives (over water) is seen for the acidic followed by polar and the aromatic residues. Further analysis suggests that the hydration layer around the protein surface is depleted more in the presence of arginine, followed by lysine and guanidine. Molecular dynamics simulations also reveal that the internal dynamics of protein, as indicated by the lifetimes of the hydrogen bonds within the protein, changes depending on the additives. Particularly, we note that the side-chain hydrogen-bonding patterns within the protein differ with the additives, with several side-chain hydrogen bonds missing in the presence of guanidine. These results collectively indicate that the aliphatic chain of arginine and lysine plays a critical role in the stabilization of the protein.

Imidazoline phosphonic acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redmore, D.

1972-07-04

Nitrogen-heterocyclic phosphonic acids and derivatives are characterized by aminomethyl (or substituted methyl) phosphonic acids or derivatives thereof bonded directly or indirectly, i.e., through a N-side chain to the nitrogen atom in the heterocyclic ring, for example those containing in the molecule at least one of the following units: ..pi..Equation/sup -/ where represents a heterocyclic ring having a nitrogen atom on the ring; -R'N- represents an amino- terminated side chain attached directly to the ring nitrogen (which side chain may or may not be present); and ..pi..Equation/sup -/ represents a methyl (or substituted methyl) phosphonic acid group where M is hydrogen,more » an alcohol or a salt moiety, and X and Y are hydrogen or a substituted group such as alkyl, aryl, etc., of which one or 2 units may be present depending on the available nitrogen bonded by hydrogens, and to uses for these compounds, for example, as scale inhibitors, corrosion inhibitors, etc. (5 claims)« less

Synthesis of Side-Chain Oxysterols and their Enantiomers through Cross-Metathesis Reactions of Δ22 Steroids

PubMed Central

Brownholland, David P.

2017-01-01

A synthetic route that utilizes a cross-metathesis reaction with Δ22 steroids has been developed to prepare sterols with varying C-27 side-chains. Natural sterols containing hydroxyl groups at the 25 and (25R)-26 positions were prepared. Enantiomers of cholesterol and (3β,25R)-26-hydroxycholesterol (27-hydroxycholesterol) trideuterated at C-19 were prepared for future biological studies. PMID:28300584

Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

PubMed

Pontikis, R; Benhida, R; Aubertin, A M; Grierson, D S; Monneret, C

1997-06-06

A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6-(arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.

Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation.

PubMed

Flemer, Stevenson; Wurthmann, Alexander; Mamai, Ahmed; Madalengoitia, José S

2008-10-03

A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.

Aqueous Processing for Printed Organic Electronics: Conjugated Polymers with Multistage Cleavable Side Chains

PubMed Central

2017-01-01

The ability to process conjugated polymers via aqueous solution is highly advantageous for reducing the costs and environmental hazards of large scale roll-to-roll processing of organic electronics. However, maintaining competitive electronic properties while achieving aqueous solubility is difficult for several reasons: (1) Materials with polar functional groups that provide aqueous solubility can be difficult to purify and characterize, (2) many traditional coupling and polymerization reactions cannot be performed in aqueous solution, and (3) ionic groups, though useful for obtaining aqueous solubility, can lead to a loss of solid-state order, as well as a screening of any applied bias. As an alternative, we report a multistage cleavable side chain method that combines desirable aqueous processing attributes without sacrificing semiconducting capabilities. Through the attachment of cleavable side chains, conjugated polymers have for the first time been synthesized, characterized, and purified in organic solvents, converted to a water-soluble form for aqueous processing, and brought through a final treatment to cleave the polymer side chains and leave behind the desired electronic material as a solvent-resistant film. Specifically, we demonstrate an organic soluble polythiophene that is converted to an aqueous soluble polyelectrolyte via hydrolysis. After blade coating from an aqueous solution, UV irradiation is used to cleave the polymer’s side chains, resulting in a solvent-resistant, electroactive polymer thin film. In application, this process results in aqueous printed materials with utility for solid-state charge transport in organic field effect transistors (OFETs), along with red to colorless electrochromism in ionic media for color changing displays, demonstrating its potential as a universal method for aqueous printing in organic electronics. PMID:28979937

Aqueous Processing for Printed Organic Electronics: Conjugated Polymers with Multistage Cleavable Side Chains.

PubMed

Schmatz, Brian; Yuan, Zhibo; Lang, Augustus W; Hernandez, Jeff L; Reichmanis, Elsa; Reynolds, John R

2017-09-27

The ability to process conjugated polymers via aqueous solution is highly advantageous for reducing the costs and environmental hazards of large scale roll-to-roll processing of organic electronics. However, maintaining competitive electronic properties while achieving aqueous solubility is difficult for several reasons: (1) Materials with polar functional groups that provide aqueous solubility can be difficult to purify and characterize, (2) many traditional coupling and polymerization reactions cannot be performed in aqueous solution, and (3) ionic groups, though useful for obtaining aqueous solubility, can lead to a loss of solid-state order, as well as a screening of any applied bias. As an alternative, we report a multistage cleavable side chain method that combines desirable aqueous processing attributes without sacrificing semiconducting capabilities. Through the attachment of cleavable side chains, conjugated polymers have for the first time been synthesized, characterized, and purified in organic solvents, converted to a water-soluble form for aqueous processing, and brought through a final treatment to cleave the polymer side chains and leave behind the desired electronic material as a solvent-resistant film. Specifically, we demonstrate an organic soluble polythiophene that is converted to an aqueous soluble polyelectrolyte via hydrolysis. After blade coating from an aqueous solution, UV irradiation is used to cleave the polymer's side chains, resulting in a solvent-resistant, electroactive polymer thin film. In application, this process results in aqueous printed materials with utility for solid-state charge transport in organic field effect transistors (OFETs), along with red to colorless electrochromism in ionic media for color changing displays, demonstrating its potential as a universal method for aqueous printing in organic electronics.

Effect of cationic side-chains on intracellular delivery and cytotoxicity of pH sensitive polymer-doxorubicin nanocarriers.

PubMed

Fang, Chen; Kievit, Forrest M; Cho, Yong-Chan; Mok, Hyejung; Press, Oliver W; Zhang, Miqin

2012-11-21

Fine-tuning the design of polymer-doxorubicin conjugates permits optimization of an efficient nanocarrier to greatly increase intracellular uptake and cytotoxicity. Here, we report synthesis of a family of self-assembled polymer-doxorubicin nanoparticles and an evaluation of the effects of various types of side-chains on intracellular uptake and cytotoxicity of the nanocarriers for lymphoma cells. Monomers with three different cationic side-chains (CA) and pK(a)'s, i.e., a guanidinium group (Ag), an imidazole group (Im), and a tertiary amine group (Dm), were comparatively investigated. The cationic monomer, poly(ethylene glycol) (PEG), and doxorubicin (Dox) were reacted with 1,4-(butanediol) diacrylate (BUDA) to prepare a poly(β-amino ester) (PBAE) polymer via Michael addition. All three polymer-Dox conjugates spontaneously formed nanoparticles (NP) through hydrophobic interactions between doxorubicin in aqueous solution, resulting in NP-Im/Dox, NP-Ag/Dox, and NP-Dm/Dox, with hydrodynamic sizes below 80 nm. Doxorubicin was linked to all 3 types of NPs with a hydrazone bond to assure selective release of doxorubicin only at acidic pH, as it occurs in the tumor microenvironment. Both NP-Im/Dox and NP-Ag/Dox exhibited much higher intracellular uptake by Ramos cells (Burkitt's lymphoma) than NP-Dm/Dox, suggesting that the type of side chain in the NPs determines the extent of intracellular uptake. As a result, NP-Im/Dox and NP-Ag/Dox showed cytotoxicity that was comparable to free Dox in vitro. Our findings suggest that the nature of surface cationic group on nanocarriers may profoundly influence their intracellular trafficking and resulting therapeutic efficacy. Thus, it is a crucial factor to be considered in the design of novel carriers for intracellular drug delivery.

Effect of cationic side-chains on intracellular delivery and cytotoxicity of pH sensitive polymer-doxorubicin nanocarriers

NASA Astrophysics Data System (ADS)

Fang, Chen; Kievit, Forrest M.; Cho, Yong-Chan; Mok, Hyejung; Press, Oliver W.; Zhang, Miqin

2012-10-01

Fine-tuning the design of polymer-doxorubicin conjugates permits optimization of an efficient nanocarrier to greatly increase intracellular uptake and cytotoxicity. Here, we report synthesis of a family of self-assembled polymer-doxorubicin nanoparticles and an evaluation of the effects of various types of side-chains on intracellular uptake and cytotoxicity of the nanocarriers for lymphoma cells. Monomers with three different cationic side-chains (CA) and pKa's, i.e., a guanidinium group (Ag), an imidazole group (Im), and a tertiary amine group (Dm), were comparatively investigated. The cationic monomer, poly(ethylene glycol) (PEG), and doxorubicin (Dox) were reacted with 1,4-(butanediol) diacrylate (BUDA) to prepare a poly(β-amino ester) (PBAE) polymer via Michael addition. All three polymer-Dox conjugates spontaneously formed nanoparticles (NP) through hydrophobic interactions between doxorubicin in aqueous solution, resulting in NP-Im/Dox, NP-Ag/Dox, and NP-Dm/Dox, with hydrodynamic sizes below 80 nm. Doxorubicin was linked to all 3 types of NPs with a hydrazone bond to assure selective release of doxorubicin only at acidic pH, as it occurs in the tumor microenvironment. Both NP-Im/Dox and NP-Ag/Dox exhibited much higher intracellular uptake by Ramos cells (Burkitt's lymphoma) than NP-Dm/Dox, suggesting that the type of side chain in the NPs determines the extent of intracellular uptake. As a result, NP-Im/Dox and NP-Ag/Dox showed cytotoxicity that was comparable to free Dox in vitro. Our findings suggest that the nature of surface cationic group on nanocarriers may profoundly influence their intracellular trafficking and resulting therapeutic efficacy. Thus, it is a crucial factor to be considered in the design of novel carriers for intracellular drug delivery.

Solvent dielectric effect and side chain mutation on the structural stability of Burkholderia cepacia lipase active site: a quantum mechanical/molecular mechanics study.

PubMed

Tahan, A; Monajjemi, M

2011-12-01

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.

Synthesis of side-chain oxysterols and their enantiomers through cross-metathesis reactions of Δ22 steroids.

PubMed

Brownholland, David P; Covey, Douglas F

2017-05-01

A synthetic route that utilizes a cross-metathesis reaction with Δ 22 steroids has been developed to prepare sterols with varying C-27 side-chains. Natural sterols containing hydroxyl groups at the 25 and (25R)-26 positions were prepared. Enantiomers of cholesterol and (3β,25R)-26-hydroxycholesterol (27-hydroxycholesterol) trideuterated at C-19 were prepared for future biological studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Enzyme resistant feruloylated xylooligomer analogues from thermochemically treated corn fiber contain large side chains, ethyl glycosides and novel sites of acetylation.

PubMed

Appeldoorn, Maaike M; de Waard, Pieter; Kabel, Mirjam A; Gruppen, Harry; Schols, Henk A

2013-11-15

In order to use corn fiber as a source for bioethanol production the enzymatic hydrolysis of the complex glucuronoarabinoxylans present has to be improved. Several oligosaccharides present in the supernatant of mild acid pretreated and enzymatically saccharified corn fiber that resist the current available enzymes were (semi)purified for structural analysis by NMR or ESI-MS(n). The structural features of 21 recalcitrant oligosaccharides are presented. A common feature of almost all these oligosaccharides is that they contain (part of) an α-l-galactopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-5-O-trans-feruloyl-l-arabinofuranose side chain attached to the O-3 position of the β-1-4 linked xylose backbone. Several of the identified oligosaccharides contained an ethyl group at the reducing end hypothesized to be formed during SSF. The ethyl glycosides found are far more complex than previously described structures. A new feature present in more than half of the oligosaccharides is an acetyl group attached to the O-2 position of the same xylose to which the oligomeric side chain was attached to the O-3 position. Finding enzymes attacking these large side chains and the dense substituted xylan backbone will boost the hydrolysis of corn fiber glucuronoxylan. Copyright © 2013 Elsevier Ltd. All rights reserved.

Complementary π-π interactions induce multicomponent coassembly into functional fibrils.

PubMed

Ryan, Derek M; Doran, Todd M; Nilsson, Bradley L

2011-09-06

Noncovalent self-assembled materials inspired by amyloid architectures are useful for biomedical applications ranging from regenerative medicine to drug delivery. The selective coassembly of complementary monomeric units to provide ordered multicomponent fibrils is a possible strategy for enhancing the sophistication of these noncovalent materials. Herein we report that complementary π-π interactions can be exploited to promote the coassembly of phenylalanine (Phe) derivatives that possess complementary aromatic side-chain functionality. Specifically, equimolar mixtures of Fmoc-Phe and Fmoc-F(5)-Phe, which possess side-chain groups with complementary quadrupole electronics, readily coassemble to form two-component fibrils and hydrogels under conditions where Fmoc-Phe alone fails to self-assemble. In addition, it was found that equimolar mixtures of Fmoc-Phe with monohalogenated (F, Cl, and Br) Fmoc-Phe derivatives also coassembled into two-component fibrils. These results collectively indicate that face-to-face quadrupole stacking between benzyl side-chain groups does not account for the molecular recognition between Phe and halogenated Phe derivatives that promote cofibrillization but that coassembly is mediated by more subtle π-π effects arising from the halogenation of the benzyl side chain. The use of complementary π-π interactions to promote the coassembly of two distinct monomeric units into ordered two-component fibrils dramatically expands the repertoire of noncovalent interactions that can be used in the development of sophisticated noncovalent materials. © 2011 American Chemical Society

Quantifying side-chain conformational variations in protein structure

PubMed Central

Miao, Zhichao; Cao, Yang

2016-01-01

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs. PMID:27845406

Quantifying side-chain conformational variations in protein structure

NASA Astrophysics Data System (ADS)

Miao, Zhichao; Cao, Yang

2016-11-01

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs.

Quantifying side-chain conformational variations in protein structure.

PubMed

Miao, Zhichao; Cao, Yang

2016-11-15

Protein side-chain conformation is closely related to their biological functions. The side-chain prediction is a key step in protein design, protein docking and structure optimization. However, side-chain polymorphism comprehensively exists in protein as various types and has been long overlooked by side-chain prediction. But such conformational variations have not been quantitatively studied and the correlations between these variations and residue features are vague. Here, we performed statistical analyses on large scale data sets and found that the side-chain conformational flexibility is closely related to the exposure to solvent, degree of freedom and hydrophilicity. These analyses allowed us to quantify different types of side-chain variabilities in PDB. The results underscore that protein side-chain conformation prediction is not a single-answer problem, leading us to reconsider the assessment approaches of side-chain prediction programs.

Interaction Enthalpy of Side Chain and Backbone Amides in Polyglutamine Solution Monomers and Fibrils.

PubMed

Punihaole, David; Jakubek, Ryan S; Workman, Riley J; Asher, Sanford A

2018-04-19

We determined an empirical correlation that relates the amide I vibrational band frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding, van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We used this correlation to determine the Q side chain carbonyl interaction enthalpy (Δ H int ) in monomeric and amyloid-like fibril conformations of D 2 Q 10 K 2 (Q10). We independently verified these Δ H int values through molecular dynamics simulations that showed excellent agreement with experiments. We found that side chain-side chain and side chain-peptide backbone interactions in fibrils and monomers are more enthalpically favorable than are Q side chain-water interactions. Q10 fibrils also showed a more favorable Δ H int for side chain-side chain interactions compared to backbone-backbone interactions. This work experimentally demonstrates that interamide side chain interactions are important in the formation and stabilization of polyQ fibrils.

From Comb-like Polymers to Bottle-Brushes

NASA Astrophysics Data System (ADS)

Liang, Heyi; Cao, Zhen; Dobrynin, Andrey; Sheiko, Sergei

We use a combination of the coarse-grained molecular dynamics simulations and scaling analysis to study conformations of bottle-brushes and comb-like polymers in a melt. Our analysis show that bottle-brushes and comb-like polymers can be in four different conformation regimes depending on the number of monomers between grafted side chains and side chain degree of polymerization. In loosely-grafted comb regime (LC) the degree of polymerization between side chains is longer than side chain degree of polymerization, such that the side chains belonging to the same macromolecule do not overlap. Crossover to a new densely-grafted comb regime (DC) takes place when side chains begin to overlap reducing interpenetration of side chains belonging to different macromolecules. In these two regimes both side-chains and backbone behave as unperturbed linear chains with the effective Kuhn length of the backbone being close to that of linear chain. Further decrease spacer degree of polymerization results in crossover to loosely-grafted bottle-brush regime (LB). In this regime, the bottle-brush backbone is stretched while the side-chains still maintain ideal chain conformation. Finally, for even shorter spacer between grafted side chains, which corresponds to densely-grafted bottle-brush regime (DB), the backbone adopts a fully extended chain conformation, and side-chains begin to stretch to maintain a constant monomer density. NSF DMR-1409710, DMR-1407645, DMR-1624569, DMR-1436201.

One-shot preparation of an inherently chiral trifunctional calix[4]arene from an easily available cone-triformylcalix[4]arene.

PubMed

Ciaccia, Maria; Tosi, Irene; Cacciapaglia, Roberta; Casnati, Alessandro; Baldini, Laura; Di Stefano, Stefano

2013-06-14

Via selective 1,3-distal intramolecular Cannizzaro disproportionation of an easily available cone-triformylcalix[4]arene, an inherently chiral trifunctional cone-calix[4]arene derivative has been prepared. The presence of three different functional groups (-CH2OH, -CHO and -COOH) at the upper rim of the calixarene scaffold makes this compound a versatile intermediate for the development of multifunctional devices. Interesting chiral discrimination of serine derivatives has been observed, presumably thanks to a multipoint-interaction involving the reversible imine bond formation and the hydrogen bonding of the hydroxyl group of the amino acid side-chain with the upper rim functional groups. Consistently, chiral discrimination was not observed with alanine and valine derivatives, lacking hydrogen bonding groups on the side-chain.

A Novel Mechanism of Sugar Selection Utilized by a Human X-family DNA Polymerase†

PubMed Central

Brown, Jessica A.; Fiala, Kevin A.; Fowler, Jason D.; Sherrer, Shanen M.; Newmister, Sean A.; Dyum, Wade W.; Suo, Zucai

2009-01-01

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2′-hydroxyl group and the bulky side chain of an active site residue. Here, we demonstrated that human DNA polymerase λ used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2′-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such a steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2′ position. PMID:19900463

Evaluating the role of acidic, basic, and polar amino acids and dipeptides on a molecular electrocatalyst for H 2 oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boralugodage, Nilusha Priyadarshani; Arachchige, Rajith Jayasingha; Dutta, Arnab

Amino acids and peptides have been shown to have a significant influence on the H2 production and oxidation reactivity of Ni(P R 2N R’ 2) 2, where P R 2N R’ 2 = 1,5-diaza-3,7-diphosphacyclooctane, R is either phenyl (Ph) or cyclohexyl (Cy), and R’ is either an amino acid or peptide. Most recently, the Ni(P Cy 2Naminoacid 2) 2 complexes (CyAA) have shown enhanced H 2 oxidation rates, water solubility, and in the case of arginine (CyArg) and phenylalanine (CyPhe), electrocatalytic reversibility. Both the backbone –COOH and side chain interactions were shown to be critical to catalytic performance. Here wemore » further investigate the roles of the outer coordination sphere by evaluating amino acids with acidic, basic, and hydrophilic side chains, as well as dipeptides which combine multiple successful features from previous complexes. Six new complexes were prepared, three containing single amino acids: aspartic acid (CyAsp), lysine (CyLys), and serine (CySer) and three containing dipeptides: glycine-phenylalanine (Cy(GlyPhe)), phenylalanine-glycine (Cy(PheGly)), and aspartic acid-phenylananine (Cy(AspPhe)). The resulting catalytic performance demonstrates that complexes need both interactions between side chain and –COOH groups for fast, efficient catalysis. The fastest of all of the catalysts, Cy(AspPhe), had both of these features, while the other dipeptide complexes with an amide replacing the -COOH were both slower; however, the amide group was demonstrated to participate in the proton pathway when side chain interactions are present to position it. Both the hydrophilic and basic side chains, notably lacking in side chain interactions, significantly increased the overpotential, with only modest increases in TOF. Of all of the complexes, only CyAsp was reversible at room temperature, and only in water, the first of these complexes to demonstrate room temperature reversibility in water. These results continue to provide and solidify design rules for controlling reactivity and efficiency of Ni(P 2N 2) 2 complexes with the outer coordination sphere.« less

Synthesis, surface characterization, and biointeraction studies of low-surface energy side-chain polyetherurethanes

NASA Astrophysics Data System (ADS)

Porter, Stephen Christopher

1999-10-01

New segmented polyetherurethanes (PEUs) with low surface energy hydrocarbon and fluorocarbon side-chains attached to the polymer hard segments were synthesized. The surface chemistry of solvent cast polymer films was studied using X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and dynamic contact angle (DCA) measurements. Increases in the overall density and length of the alkyl side-chains within the PEUs resulted in greater side-chain concentrations at the polymer surface. PEUs bearing long alkyl (> C10 ) and perfluorocarbon side-chains were found to posses surfaces with highly enriched side-chain concentrations relative to the bulk polymer. In PEUs with significant side-chain surface enrichment, the relatively polar hard segment blocks were shown to reside in high concentrations just below the side-chain enriched surface layer. Furthermore, DCA measurements demonstrated that the surface of the alkyl side-chain PEUs did not undergo significant rearrangement when placed into an aqueous environment, whereas the surface of a hard segment model polymer bearing C18 sidechains (PEU-C18-HS) did. Hydrogen bonding within the PEUs was examined using FTIR and was shown to be disrupted by the addition of side-chains; an effect dependent on the density but not on the length of the side-chains. Heteropolymer blends comprised of mixtures of high side-chain density and side-chain free PEUs were compared with homopolymers having the same overall side-chain concentration as the blends. Significantly more surface enrichment of side-chains was found in the heteropolymer blends whereas hydrogen bonding nearly the same as in the homopolymers. Adsorption of native and delipidized human serum albumin (HSA) from pure solution and blood plasma; the elutabilty of adsorbed HSA; and static platelet adhesion to plasma preadsorbed surfaces, were all examined on alkyl side-chain PEUs. Several polymers with high C18 side-chain densities displayed increased affinity for albumin, and reduced elutability. Among these, PEU-C18-HS demonstrated a significant reduction in platelet adhesion at low plasma pre-adsorption concentrations. However, competitive binary adsorption of fibrinogen in the presence of HSA demonstrated lower relative albumin affinity for PEU-C18-HS than other PEUs. The observed effects are thought to be mainly a result of increased surface hydrophobicity of the alkyl-side chain modified PEU, and not high specificity albumin binding.

From globules to crystals: a spectral study of poly(2-isopropyl-2-oxazoline) crystallization in hot water.

PubMed

Sun, Shengtong; Wu, Peiyi

2015-12-28

One easy strategy to comprehend the complex folding/crystallization behaviors of proteins is to study the self-assembly process of their synthetic polymeric analogues with similar properties owing to their simple structures and easy access to molecular design. Poly(2-isopropyl-2-oxazoline) (PIPOZ) is often regarded as an ideal pseudopeptide with similar two-step crystallization behavior to proteins, whose aqueous solution experiences successive lower critical solution temperature (LCST)-type liquid-liquid phase separation upon heating and irreversible crystallization when annealed above LCST for several hours. In this paper, by microscopic observations, IR and Raman spectroscopy in combination with 2D correlation analysis, we show that the second step of PIPOZ crystallization in hot water can be further divided into two apparent stages, i.e., nucleation and crystal growth, and perfect crystalline PIPOZ chains are found to only develop in the second stage. While all the groups exhibit changes in initial nucleation, only methylene groups on the backbone participate in the crystal growth stage. During nucleation, a group motion transfer is found from the side chain to the backbone, and nucleation is assumed to be mainly driven by the cleavage of bridging C=O···D-O-D···O=C hydrogen bonds followed by chain arrangement due to amide dipolar orientation. Nevertheless, during crystal growth, a further chain ordering process occurs resulting in the final formation of crystalline PIPOZ chains with partial trans conformation of backbones and alternative side chains on the two sides. The underlying crystallization mechanism of PIPOZ in hot water we present here may provide very useful information for understanding the crystallization of biomacromolecules in biological systems.

Hydration of non-polar anti-parallel β-sheets

NASA Astrophysics Data System (ADS)

Urbic, Tomaz; Dias, Cristiano L.

2014-04-01

In this work we focus on anti-parallel β-sheets to study hydration of side chains and polar groups of the backbone using all-atom molecular dynamics simulations. We show that: (i) water distribution around the backbone does not depend significantly on amino acid sequence, (ii) more water molecules are found around oxygen than nitrogen atoms of the backbone, and (iii) water molecules around nitrogen are highly localized in the planed formed by peptide backbones. To study hydration around side chains we note that anti-parallel β-sheets exhibit two types of cross-strand pairing: Hydrogen-Bond (HB) and Non-Hydrogen-Bond (NHB) pairing. We show that distributions of water around alanine, leucine, and valine side chains are very different at HB compared to NHB faces. For alanine pairs, the space between side chains has a higher concentration of water if residues are located in the NHB face of the β-sheet as opposed to the HB face. For leucine residues, the HB face is found to be dry while the space between side chains at the NHB face alternates between being occupied and non-occupied by water. Surprisingly, for valine residues the NHB face is dry, whereas the HB face is occupied by water. We postulate that these differences in water distribution are related to context dependent propensities observed for β-sheets.

Hydration of non-polar anti-parallel β-sheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbic, Tomaz; Dias, Cristiano L., E-mail: cld@njit.edu

2014-04-28

In this work we focus on anti-parallel β-sheets to study hydration of side chains and polar groups of the backbone using all-atom molecular dynamics simulations. We show that: (i) water distribution around the backbone does not depend significantly on amino acid sequence, (ii) more water molecules are found around oxygen than nitrogen atoms of the backbone, and (iii) water molecules around nitrogen are highly localized in the planed formed by peptide backbones. To study hydration around side chains we note that anti-parallel β-sheets exhibit two types of cross-strand pairing: Hydrogen-Bond (HB) and Non-Hydrogen-Bond (NHB) pairing. We show that distributions ofmore » water around alanine, leucine, and valine side chains are very different at HB compared to NHB faces. For alanine pairs, the space between side chains has a higher concentration of water if residues are located in the NHB face of the β-sheet as opposed to the HB face. For leucine residues, the HB face is found to be dry while the space between side chains at the NHB face alternates between being occupied and non-occupied by water. Surprisingly, for valine residues the NHB face is dry, whereas the HB face is occupied by water. We postulate that these differences in water distribution are related to context dependent propensities observed for β-sheets.« less

Phenylalanine 445 within oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae influences C-Ring cyclization and deprotonation reactions.

PubMed

Wu, Tung-Kung; Liu, Yuan-Ting; Chiu, Feng-Hsuan; Chang, Cheng-Hsiang

2006-10-12

[reaction: see text] We describe the Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase Phe445 site-saturated mutants that generate truncated tricyclic and altered deprotonation product profiles. Among these mutants, only polar side-chain group substitutions genetically complemented yeast viability and produced spatially related product diversity, supporting the Johnson model that cation-pi interactions between a carbocationic intermediate and an enzyme can be replaced by an electrostatic or polar side chain to stabilize the cationic intermediate, but with product differentiation.

Study of methyl- and phenyl-substituted thermostable polysiloxane-silarylene motionless phases for capillary gas chromatography

NASA Astrophysics Data System (ADS)

Komarova, A. O.; Shashkov, M. V.; Sidel'nikov, V. N.

2017-11-01

Capillary columns based on a number of thermostable polysiloxane-silarylene motionless phases are prepared and their properties are studied. Three polymers with different contents of methyl and phenyl groups are synthesized: dimethylsiloxanesilarylene (DMS), methylphenylsiloxanesilarylene (MPhS), and diphenylsiloxanesilarylene (DPhS). Studies of their thermostability show that the level of the background current of these columns upon heating to 350°C is several times lower than that of a column based on polydimethylsiloxane. Based on McReynolds' studies of polarity and Abraham's studies of the selectivity of prepared columns according to the parameters of intermolecular interactions, it is found that silarylene MLPs are more affected by the contributions from specific interactions (especially for dipole-dipole, π-π-, and n-π-interactions) than MLPs with no phenylene inserts. The effect on the selectivity of a phenyl group inside a chain differs from the one produced by the phenyl groups in side MLP chains. The effect on the selectivity of a phenyl group inside a chain differs from the one produced by the phenyl groups in side MLP chains. Examples of the separation of test mixtures of aromatic and oxygen-containing compounds are obtained, along with an extract of thistle oil containing tocopherols and phytosterols at a final temperature of analysis of 350°C.

Poly[(arylene ethynylene)-alt-(arylene vinylene)]s Based on Anthanthrone and Its Derivatives: Synthesis and Photophysical, Electrochemical, Electroluminescent, and Photovoltaic Properties

PubMed Central

2017-01-01

Anthanthrone and its derivatives are large polycyclic aromatic compounds (PACs) that pose a number of challenges for incorporation into the structure of soluble conjugated polymers. For the first time, this group of PACs was employed as the building blocks for the synthesis of copolymers (P1–P5) based on poly[(arylene ethynylene)-alt-(arylene vinylene)]s backbone (−Ph–C≡C–Anth–C≡C–Ph–CH=CH–Ph–CH=CH−)n. During the synthesis of P1–P5, different alkyloxy side chains were incorporated in order to tune the properties of the polymers. Of the copolymer series only P1 (containing anthanthrone and branched 2-ethylhexyloxy side chains on phenylenes), P2 and P3 (for which the anthanthrones containing carbonyl groups were converted to anthanthrene containing alkyloxy substituents) were soluble. The photophysical, electrochemical, electroluminescent and photovoltaic properties of P1–P3 are reported, compared and discussed with respect to the effects of side chains. PMID:29151617

TROSY of side-chain amides in large proteins

PubMed Central

Liu, Aizhuo; Yao, Lishan; Li, Yue; Yan, Honggao

2012-01-01

By using the mixed solvent of 50% H2O/50% D2O and employing deuterium decoupling, TROSY experiments exclusively detect NMR signals from semideuterated isotopomers of carboxamide groups with high sensitivities for proteins with molecular weights up to 80 kDa. This isotopomer-selective strategy extends TROSY experiments from exclusively detecting backbone to both backbone and side-chain amides, particularly in large proteins. Because of differences in both TROSY effect and dynamics between 15N–HE{DZ} and 15N–HZ{DE} isotopomers of the same carboxamide, the 15N transverse magnetization of the latter relaxes significantly faster than that of the former, which provides a direct and reliable stereospecific distinction between the two configurations. The TROSY effects on the 15N–HE{DZ} isotopomers of side-chain amides are as significant as on backbone amides. PMID:17347000

Thermodynamic Interactions between Polystyrene and Long-Chain Poly(n-Alkyl Acrylates) Derived from Plant Oils.

PubMed

Wang, Shu; Robertson, Megan L

2015-06-10

Vegetable oils and their fatty acids are promising sources for the derivation of polymers. Long-chain poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) are readily derived from fatty acids through conversion of the carboxylic acid end-group to an acrylate or methacrylate group. The resulting polymers contain long alkyl side-chains with around 10-22 carbon atoms. Regardless of the monomer source, the presence of alkyl side-chains in poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) provides a convenient mechanism for tuning their physical properties. The development of structured multicomponent materials, including block copolymers and blends, containing poly(n-alkyl acrylates) and poly(n-alkyl methacrylates) requires knowledge of the thermodynamic interactions governing their self-assembly, typically described by the Flory-Huggins interaction parameter χ. We have investigated the χ parameter between polystyrene and long-chain poly(n-alkyl acrylate) homopolymers and copolymers: specifically we have included poly(stearyl acrylate), poly(lauryl acrylate), and their random copolymers. Lauryl and stearyl acrylate were chosen as model alkyl acrylates derived from vegetable oils and have alkyl side-chain lengths of 12 and 18 carbon atoms, respectively. Polystyrene is included in this study as a model petroleum-sourced polymer, which has wide applicability in commercially relevant multicomponent polymeric materials. Two independent methods were employed to measure the χ parameter: cloud point measurements on binary blends and characterization of the order-disorder transition of triblock copolymers, which were in relatively good agreement with one another. The χ parameter was found to be independent of the alkyl side-chain length (n) for large values of n (i.e., n > 10). This behavior is in stark contrast to the n-dependence of the χ parameter predicted from solubility parameter theory. Our study complements prior work investigating the interactions between polystyrene and short-chain polyacrylates (n ≤ 10). To our knowledge, this is the first study to explore the thermodynamic interactions between polystyrene and long-chain poly(n-alkyl acrylates) with n > 10. This work lays the groundwork for the development of multicomponent structured systems (i.e., blends and copolymers) in this class of sustainable materials.

An improved approach to the analysis of drug-protein binding by distance geometry

NASA Technical Reports Server (NTRS)

Goldblum, A.; Kieber-Emmons, T.; Rein, R.

1986-01-01

The calculation of side chain centers of coordinates and the subsequent generation of side chain-side chain and side chain-backbone distance matrices is suggested as an improved method for viewing interactions inside proteins and for the comparison of protein structures. The use of side chain distance matrices is demonstrated with free PTI, and the use of difference distance matrices for side chains is shown for free and trypsin-bound PTI as well as for the X-ray structures of trypsin complexes with PTI and with benzamidine. It is found that conformational variations are reflected in the side chain distance matrices much more than in the standard C-C distance representations.

Antithrombogenic Polymer Coating.

DOEpatents

Huang, Zhi Heng; McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

2003-01-21

An article having a non-thrombogenic surface and a process for making the article are disclosed. The article is formed by (i) coating a polymeric substrate with a crosslinked chemical combination of a polymer having at least two amino substituted side chains, a crosslinking agent containing at least two crosslinking functional groups which react with amino groups on the polymer, and a linking agent containing a first functional group which reacts with a third functional group of the crosslinking agent, and (ii) contacting the coating on the substrate with an antithrombogenic agent which covalently bonds to a second functional group of the linking agent. In one example embodiment, the polymer is a polyamide having amino substituted alkyl chains on one side of the polyamide backbone, the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl, the linking agent is a polyhydrazide and the antithrombogenic agent is heparin.

Relaxation spectra and dipolar correlations for flexible polymers with bulky side groups

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz-Calleja, R.; Riande, E.; Roman, J.S.

1992-08-06

This paper discusses how relaxation spectra and dipolar correlations for flexible polymers with bulky side groups (PBPA chains) suggest that intermolecular correlations are not very important in this polymer and that {alpha}, {beta}, and {gamma} absorptions exist. TSDC techniques reveal that the {gamma} peak has a smaller activation energy than the {beta}, and the coupling scheme is used to interpret the complex dielectric and mechanical {alpha} relaxations. The anomalous temperature dependence of the glass-rubber relaxation is discussed in terms of the bulkiness of the side group. 23 refs., 8 figs., 3 tabs.

The solvatochromic effects of side chain substitution on the binding interaction of novel tricarbocyanine dyes with human serum albumin.

PubMed

Beckford, Garfield; Owens, Eric; Henary, Maged; Patonay, Gabor

2012-04-15

The effects of solvatochromism on protein-ligand interactions have been studied by absorbance and near-infrared laser induced fluorescence (NIR-LIF) spectroscopy. The utility of three novel classes of cyanine dyes designed for this purpose illustrates that the affinity interactions of ligands at the hydrophobic binding pockets of Human Serum Albumin (HSA) are not only dependent on the overall hydrophobic characteristics of the molecules but are highly influenced by the size of the ligands as well. Whereas changes to the chromophore moiety exhibited slight to moderate changes to the hydrophobic nature of these molecules, substitution at the alkyl indolium side chain has enabled us to vary the binding affinity towards serum albumin. Substitution at the indolium side chain among an ethyl to butyl group results in improved binding characteristics and an almost three-fold increase in affinity constant. In addition, replacement of the ethyl side chain with a phenylpropyl group also yielded unique solvotachromic patterns such as increased hydrophobicity and subsequent biocompatibility with the HSA binding regions. Ligand interaction was however inhibited by steric hindrance associated with the bulky phenyl ring system thus affecting the increased binding that could be realized from the improved hydrophobic nature of the molecules. This characteristic change in binding affinity is of potential interest to developing a methodology which reveals information on the hydrophobic character and steric specificity of the binding cavities. Copyright © 2012 Elsevier B.V. All rights reserved.

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giovannitti, Alexander; Maria, Iuliana P.; Hanifi, David

Here, we report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performancemore » in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.« less

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes.

PubMed

Giovannitti, Alexander; Maria, Iuliana P; Hanifi, David; Donahue, Mary J; Bryant, Daniel; Barth, Katrina J; Makdah, Beatrice E; Savva, Achilleas; Moia, Davide; Zetek, Matyáš; Barnes, Piers R F; Reid, Obadiah G; Inal, Sahika; Rumbles, Garry; Malliaras, George G; Nelson, Jenny; Rivnay, Jonathan; McCulloch, Iain

2018-05-08

We report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performance in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes

DOE PAGES

Giovannitti, Alexander; Maria, Iuliana P.; Hanifi, David; ...

2018-04-24

Here, we report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performancemore » in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.« less

A novel mechanism of sugar selection utilized by a human X-family DNA polymerase.

PubMed

Brown, Jessica A; Fiala, Kevin A; Fowler, Jason D; Sherrer, Shanen M; Newmister, Sean A; Duym, Wade W; Suo, Zucai

2010-01-15

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2'-hydroxyl group and the bulky side chain of an active-site residue. In this study, we demonstrated that human DNA polymerase lambda used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2'-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2'-position. Copyright 2009 Elsevier Ltd. All rights reserved.

Roles of head group architecture and side chain length on colorimetric response of polydiacetylene vesicles to temperature, ethanol and pH.

PubMed

Charoenthai, Nipaphat; Pattanatornchai, Thanutpon; Wacharasindhu, Sumrit; Sukwattanasinitt, Mongkol; Traiphol, Rakchart

2011-08-15

In this contribution, we report the relationship between molecular structures of polydiacetylene (PDA) vesicles, fabricated by using three monomers, 10,12-tricosadiynoic acid (TCDA), 10,12-pentacosadiynoic acid (PCDA) and N-(2-aminoethyl)pentacosa-10,12-diynamide (AEPCDA), and their color-transition behaviors. The modification of side chain length and head group of the PDA vesicles strongly affects the colorimetric response to temperature, ethanol and pH. A shorter side chain of poly(TCDA) yields weaker inter- and intra-chain dispersion interactions in the bilayers compared to the system of poly(PCDA), which in turn results in a faster color transition upon exposure to all stimuli. A change of head group in poly(AEPCDA) slightly reduces the transition temperature. Interestingly, the colorimetric response of poly(AEPCDA) vesicles to the addition of ethanol is found to occur in a two-step fashion while the response of poly(PCDA) vesicles takes place in a one-step process. The amount of ethanol required for inducing complete color-transition of poly(AEPCDA) vesicles is also much higher, about 87% v/v. The increase of pH to ~9 and ~10 causes a color-transition of poly(TCDA) and poly(PCDA) vesicles, respectively. The poly(AEPCDA) vesicles, on the other hand, change color upon decreasing pH to ~0. The colorimetric response also occurs in a multi-step fashion. These discrepancies are attributed to the architecture of surface layers of poly(AEPCDA), constituting amine and amide groups separated by ethyl linkers. Copyright © 2011 Elsevier Inc. All rights reserved.

Ionization and order disorder transition of hydrogels with ionizable hydrophobic side chain

NASA Astrophysics Data System (ADS)

Matsuda, A.; Katayama, Y.; Kaneko, T.; Gong, J. P.; Osada, Y.

2000-10-01

pH dependence of the structural change of the amphiphilic copolymer gels containing the crystallizable side chain with carboxylic end group, poly(16-acryloylhexadecanoic acid (AHA)- co-acrylic acid (AA)), has been investigated. The poly(AHA- co-AA) gels could maintain the crystalline domain of AHA units up to pH=11 at ambient temperature, which abruptly transferred into disordered state beyond this pH due to the dissociation of the carboxylic group of AHA. However, the addition of salt or divalent ion enabled to crystallize the gel even at pH=11.5 due to the effective shielding of the electrostatic repulsion. The mechanism of order-disorder transition through changes of pH and salt concentration was discussed in terms of association-dissociation of AHA groups.

Amphiphilic polymer based on fluoroalkyl and PEG side chains for fouling release coating

NASA Astrophysics Data System (ADS)

Cong, W. W.; Wang, K.; Yu, X. Y.; Zhang, H. Q.; Lv, Z.; Gui, T. J.

2017-12-01

Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

Molecular structures and antiproliferative activity of side-chain saturated and homologated analogs of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone

NASA Astrophysics Data System (ADS)

Pal, Sanjima; Jadhav, Mahesh; Weyhermüller, Thomas; Patil, Yogesh; Nethaji, M.; Kasabe, Umesh; Kathawate, Laxmi; Konkimalla, V. Badireenath; Salunke-Gawali, Sunita

2013-10-01

Side chain homologated derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinone {n-alkyl: pentyl; L-5, hexyl; L-6, heptyl; L-7 and octyl; L-8} have been synthesized and characterized by elemental analysis, FT-IR, 1H NMR, UV-visible spectroscopy and LC-MS. Compounds, L-4, {n-alkyl: butyl; L-4}, L-6 and L-8 have been characterized by single crystal X-ray diffraction studies. The single crystal X-ray structures reveal that L-4 and L-8 crystallizes in P21 space group, while L-6 in P21/c space group. Molecules of L-4 and L-8 from polymeric chains through Csbnd H⋯O and Nsbnd H⋯O close contacts. L-6 is a dimer formed by Nsbnd H⋯O interaction. Slipped π-π stacking interactions are observed between quinonoid and benzenoid rings of L-4 and L-8. Orientations of alkyl group in L-4 and L-8 is on same side of the chain and polymeric chains run opposite to one another to form zip like structure to the alkyl groups. Antiproliferative activities of L-1 to L-8{n-alkyl: methyl; L-1, ethyl; L-2, propyl; L-3 and butyl; L-4} were studied in cancer cells of colon (COLO205), brain (U87MG) and pancreas (MIAPaCa2) where L-1, L-2 and L-3 were active in MIAPaCa2 (L-1 = L-2 > L-3) and COLO205 (L-2 = L-3 > L-1) and inactive in U87MG. From antiproliferative studies with compounds L-1 to L-8 it can be concluded that homologation of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone with saturated methyl groups yielded tissue specific compounds such as L-2 (for MIAPaCa2) and L-3 (for COLO205) with optimal activity.

Solvation thermodynamics of amino acid side chains on a short peptide backbone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hajari, Timir; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de

The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvationmore » free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side chain cavities in bulk water, in agreement with earlier work in the literature on analysis of cavity fluctuations at nonpolar molecular surfaces. The cavity and dispersion interaction contributions correlate quite well with the solvent accessible surface area of the nonpolar side chains attached to the backbone. This correlation however is weak for the overall solvation free energies owing to the fact that the cavity and dispersion free energy contributions are almost exactly cancelling each other.« less

Solvation thermodynamics of amino acid side chains on a short peptide backbone

NASA Astrophysics Data System (ADS)

Hajari, Timir; van der Vegt, Nico F. A.

2015-04-01

The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvation free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side chain cavities in bulk water, in agreement with earlier work in the literature on analysis of cavity fluctuations at nonpolar molecular surfaces. The cavity and dispersion interaction contributions correlate quite well with the solvent accessible surface area of the nonpolar side chains attached to the backbone. This correlation however is weak for the overall solvation free energies owing to the fact that the cavity and dispersion free energy contributions are almost exactly cancelling each other.

Point mutations abolishing the mannose-binding capability of boar spermadhesin AQN-1.

PubMed

Ekhlasi-Hundrieser, Mahnaz; Calvete, Juan J; Von Rad, Bettina; Hettel, Christiane; Nimtz, Manfred; Töpfer-Petersen, Edda

2008-05-01

The mannose-binding capability of recombinant wild-type boar spermadhesin AQN-1 and of its site-directed mutants in the highly-conserved region around of the single glycosylation site (asparagine 50) of some spermadhesins, where the carbohydrate binding site has been proposed to be located, was checked using a solid-phase assay and a biotinylated mannose ligand. Substitution of glycine 54 by amino acids bearing an unipolar side chain did not cause significant decrease in the mannose-binding activity. However, amino acids with uncharged polar side chains or having a charged polar side chain abolished the binding of biotinylated mannose to the corresponding AQN-1 mutants. The results suggest that the higher surface accessibility of amino acids possessing polar side chains compared to those bearing nonpolar groups may sterically interfere with monosaccharide binding. The location of the mannose-binding site in AQN-1 appears to be topologically conserved in other heparin-binding boar spermadhesins, i.e., AQN-3 and AWN, but departs from the location of the mannose-6-phosphate-recognition site of PSP-II. This indicates that different spermadhesin molecules have evolved non-equivalent carbohydrate-binding capabilities, which may underlie their distinct patterns of biological activities.

Novel synthesis of cyclic amide-linked analogues of angiotensins II and III.

PubMed

Matsoukas, J M; Hondrelis, J; Agelis, G; Barlos, K; Gatos, D; Ganter, R; Moore, D; Moore, G J

1994-09-02

Cyclic amide-linked angiotension II (ANGII) analogues have been synthesized by novel strategies, in an attempt to test the ring clustering and the charge relay bioactive conformation recently suggested. These analogues were synthesized by connecting side chain amino and carboxyl groups at positions 1 and 8, 2 and 8, 3 and 8, and 3 and 5, N-terminal amino and C-terminal carboxyl groups at positions 1 and 8, 2 and 8, and 4 and 8, and side chain amino to C-terminal carboxyl group at positions 1 and 8. All these analogues were biologically inactive, except for cyclic [Sar1, Asp3, Lys5]ANGII (analogue 10) which had high contractile activity in the rat uterus assay (30% of ANGII) and [Lys1, Tyr(Me)4, Glu8]ANGII (analogue 7) which had weak antagonist activity (PA2 approximately 6). Precyclic linear peptides synthesized using 2-chlorotrityl chloride resin and N alpha-Fmoc-amino acids with suitable side chain protection were obtained in high yield and purity and were readily cyclized with benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate as coupling reagent. Molecular modeling suggests that the ring structure of the potent analogue can be accommodated in the charge relay conformation proposed for ANGII.

SCit: web tools for protein side chain conformation analysis.

PubMed

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

The cysteine 34 residue of A1M/α1-microglobulin is essential for protection of irradiated cell cultures and reduction of carbonyl groups.

PubMed

Rutardottir, S; Nilsson, E J C; Pallon, J; Gram, M; Åkerström, B

2013-07-01

α1-microglobulin (A1M) is a 26 kDa plasma and a tissue protein belonging to the lipocalin family. The reductase and free radical scavenger A1M has been shown to protect cells and extracellular matrix against oxidative and irradiation-induced damage. The reductase activity was previously shown to depend upon an unpaired cysteinyl side-chain, C34, and three lysyl side-chains, K92, 118, and 130, located around the open end of the lipocalin pocket. The aim of this work was to investigate whether the cell and matrix protection by A1M is a result of its reductase activity by using A1M-variants with site-directed mutations of the C34, K92, K118, and K130 positions. The results show that the C34 side-chain is an absolute requirement for protection of HepG2 cell cultures against alpha-particle irradiation-induced cell death, upregulation of stress response and cell cycle regulation genes. Mutation of C34 also resulted in loss of the reduction capacity toward heme- and hydrogen peroxide-oxidized collagen, and the radical species 2,2´-azino-bis (3-ethyl-benzo-thiazoline-6-sulphonic acid) (ABTS). Furthermore, mutation of C34 significantly suppressed the cell-uptake of A1M. The K92, K118, and K130 side-chains were of minor importance in cell protection and reduction of oxidized collagen but strongly influenced the reduction of the ABTS-radical. It is concluded that antioxidative protection of cells and collagen by A1M is totally dependent on its C34 amino acid residue. A model of the cell protection mechanism of A1M should be based on the redox activity of the free thiolyl group of the C34 side-chain and a regulatory role of the K92, K118, and K130 residues.

Biodegradation of lignin by Agaricus Bisporus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vane, C.H.; Abbott, G.D.; Head, I.M.

The lignolytic activity of Agaricus bisporus will be addressed in this paper. Sound and fungally degraded lignins were characterized by Pyrolysis-Gas Chromatography-Mass Spectrometry (Py-GC-MS), Fourier Transform Infrared Spectroscopy (FnR) and elemental analysis. Fungally degraded lignins displayed increased wt%N, wt%H and wt%O content and decreased wt%C content The FTIR spectrum of decayed lignin showed an increase in the relative intensity of absorption bands assigned to carbonyl and carboxyl functional groups located on the aliphatic side chain and a decrease in absorption bands assigned to aromatic skeletal vibration modes. Semiquantitative Py-GC-MS revealed an 82% decrease in lignin derived pyrolysis products upon biodegradation.more » No significant increase in pyrolysis products with an oxygenated aliphatic side chain were detected in the fungally degraded lignin however shortening of the aliphatic side chain via cleavage at the {alpha}, {beta} and {gamma} positions was observed.« less

Side-chain Engineering of Benzo[1,2-b:4,5-b’]dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells

PubMed Central

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-01-01

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b’]dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing. PMID:27140224

Side-chain Engineering of Benzo[1,2-b:4,5-b']dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells.

PubMed

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-05-03

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b']dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing.

Pharmacophore mapping in the laulimalide series: total synthesis of a vinylogue for a late-stage metathesis diversification strategy.

PubMed

Wender, Paul A; Hilinski, Michael K; Skaanderup, Philip R; Soldermann, Nicolas G; Mooberry, Susan L

2006-08-31

An efficient synthesis of the macrocyclic core of laulimalide with a pendant vinyl group at C20 is described, allowing for late-stage introduction of various side chains through a selective and efficient cross metathesis diversification step. Representative analogues reported herein are the first to contain modifications to only the side chain dihydropyran of laulimalide and des-epoxy laulimalide. This step-economical strategy enables the rapid synthesis of new analogues using alkenes as an inexpensive, abundantly available diversification feedstock.

Organization of pectic arabinan and galactan side chains in association with cellulose microfibrils in primary cell walls and related models envisaged.

PubMed

Zykwinska, Agata; Thibault, Jean-François; Ralet, Marie-Christine

2007-01-01

The structure of arabinan and galactan domains in association with cellulose microfibrils was investigated using enzymatic and alkali degradation procedures. Sugar beet and potato cell wall residues (called 'natural' composites), rich in pectic neutral sugar side chains and cellulose, as well as 'artificial' composites, created by in vitro adsorption of arabinan and galactan side chains onto primary cell wall cellulose, were studied. These composites were sequentially treated with enzymes specific for pectic side chains and hot alkali. The degradation approach used showed that most of the arabinan and galactan side chains are in strong interaction with cellulose and are not hydrolysed by pectic side chain-degrading enzymes. It seems unlikely that isolated arabinan and galactan chains are able to tether adjacent microfibrils. However, cellulose microfibrils may be tethered by different pectic side chains belonging to the same pectic macromolecule.

On the specificity of a bacteriophage-borne endoglycanase for the native capsular polysaccharide produced by Klebsiella pneumoniae SK1 and its derived polymers.

PubMed

Cescutti, P; Paoletti, S

1994-02-15

The specificity of the endoglycanase associated with the bacteriophage phi SK1 particles was tested on the native capsular polysaccharide produced by Klebsiella pneumoniae serotype SK1 and on three chemically modified polymers derived from it. The primary structure of the SK1 capsular polysaccharide is: [formula: see text] and the beta 1-3 linkage between the glucose and the galactose residues is the one cleaved by the phage enzyme. The enzyme activity was assayed on the deacetylated polysaccharide and on two derivatives obtained by removal of both the side-chain sugars and of only the alpha-D-galactosyl unit, respectively. The endoglycanase was more active on the deacetylated polysaccharide than on the native one, suggesting that the presence of the acetyl groups interferes with the enzyme-polysaccharide interaction. A possible role of the acetyl groups in the control of the polysaccharide chain length and hence on the rheological behaviour of the capsule cannot be ruled out, as already indicated for other bacterial polysaccharides. On the contrary, the removal of the side chains, either complete or selective, caused the modification of the recognition site in such a way that the enzymatic depolymerization no longer occurred. Therefore, it can be inferred that the phi SK1 endoglycanase requires the presence of both the side chain sugars to exhibit its cleaving activity, although this latter is in the main chain.

Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

PubMed

Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

2014-01-01

Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

Side-chain mobility in the folded state of Myoglobin

NASA Astrophysics Data System (ADS)

Lammert, Heiko; Onuchic, Jose

We study the accessibility of alternative side-chain rotamer configurations in the native state of Myoglobin, using an all-atom structure-based model. From long, unbiased simulation trajectories we determine occupancies of rotameric states and also estimate configurational and vibrational entropies. Direct sampling of the full native-state dynamics, enabled by the simple model, reveals facilitation of side-chain motions by backbone dynamics. Correlations between different dihedral angles are quantified and prove to be weak. We confirm global trends in the mobilities of side-chains, following burial and also the chemical character of residues. Surface residues loose little configurational entropy upon folding; side-chains contribute significantly to the entropy of the folded state. Mobilities of buried side-chains vary strongly with temperature. At ambient temperature, individual side-chains in the core of the protein gain substantial access to alternative rotamers, with occupancies that are likely observable experimentally. Finally, the dynamics of buried side-chains may be linked to the internal pockets, available to ligand gas molecules in Myoglobin.

Residues with similar hexagon neighborhoods share similar side-chain conformations.

PubMed

Li, Shuai Cheng; Bu, Dongbo; Li, Ming

2012-01-01

We present in this study a new approach to code protein side-chain conformations into hexagon substructures. Classical side-chain packing methods consist of two steps: first, side-chain conformations, known as rotamers, are extracted from known protein structures as candidates for each residue; second, a searching method along with an energy function is used to resolve conflicts among residues and to optimize the combinations of side chain conformations for all residues. These methods benefit from the fact that the number of possible side-chain conformations is limited, and the rotamer candidates are readily extracted; however, these methods also suffer from the inaccuracy of energy functions. Inspired by threading and Ab Initio approaches to protein structure prediction, we propose to use hexagon substructures to implicitly capture subtle issues of energy functions. Our initial results indicate that even without guidance from an energy function, hexagon structures alone can capture side-chain conformations at an accuracy of 83.8 percent, higher than 82.6 percent by the state-of-art side-chain packing methods.

SCit: web tools for protein side chain conformation analysis

PubMed Central

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit. PMID:15215438

The binding of analogs of porphyrins and chlorins with elongated side chains to albumin

PubMed Central

Ben Dror, Shimshon; Bronshtein, Irena; Weitman, Hana; Smith, Kevin M.; O’Neal, William G.; Jacobi, Peter A.; Ehrenberg, Benjamin

2012-01-01

In previous studies, we demonstrated that elongation of side chains of several sensitizers endowed them with higher affinity for artificial and natural membranes and caused their deeper localization in membranes. In the present study, we employed eight hematoporphyrin and protoporphyrin analogs and four groups containing three chlorin analogs each, all synthesized with variable numbers of methylenes in their alkyl carboxylic chains. We show that these tetrapyrroles’ affinity for bovine serum albumin (BSA) and their localization in the binding site are also modulated by chain lengths. The binding constants of the hematoporphyrins and protoporphyrins to BSA increased as the number of methylenes was increased. The binding of the chlorins depended on the substitution at the meso position opposite to the chains. The quenching of the sensitizers’ florescence by external iodide ions decreased as the side chains became longer, indicating to deeper insertion of the molecules into the BSA binding pocket. To corroborate this conclusion, we studied the efficiency of photodamage caused to tryptophan in BSA upon illumination of the bound sensitizers. The efficiency was found to depend on the side-chain lengths of the photosensitizer. We conclude that the protein site that hosts these sensitizers accommodates different analogs at positions that differ slightly from each other. These differences are manifested in the ease of access of iodide from the external aqueous phase, and in the proximity of the photosensitizers to the tryptophan. In the course of this study, we developed the kinetic equations that have to be employed when the sensitizer itself is being destroyed. PMID:19330323

The introduction of strain and its effects on the structure and stability of T4 lysozyme.

PubMed

Liu, R; Baase, W A; Matthews, B W

2000-01-07

In order to try to better understand the role played by strain in the structure and stability of a protein a series of "small-to-large" mutations was made within the core of T4 lysozyme. Three different alanine residues, one involved in backbone contacts, one in side-chain contacts, and the third adjacent to a small cavity, were each replaced with subsets of the larger residues, Val, Leu, Ile, Met, Phe and Trp. As expected, the protein is progressively destabilized as the size of the introduced side-chain becomes larger. There does, however, seem to be a limit to the destabilization, suggesting that a protein of a given size may be capable of maintaining only a certain amount of strain. The changes in stability vary greatly from site to site. Substitution of larger residues for both Ala42 and Ala98 substantially destabilize the protein, even though the primary contacts in one case are predominantly with side-chain atoms and in the other with backbone. The results suggest that it is neither practical nor meaningful to try to separate the effects of introduced strain on side-chains from the effects on the backbone. Substitutions at Ala129 are much less destabilizing than at sites 42 or 98. This is most easily understood in terms of the pre-existing cavity, which provides partial space to accommodate the introduced side-chains. Crystal structures were obtained for a number of the mutants. These show that the changes in structure to accommodate the introduced side-chains usually consist of essentially rigid-body displacements of groups of linked atoms, achieved through relatively small changes in torsion angles. On rare occasions, a side-chain close to the site of substitution may change to a different rotamer. When such rotomer changes occur, they permit the structure to dissipate strain by a response that is plastic rather than elastic. In one case, a surface loop moves 1.2 A, not in direct response to a mutation, but in an interaction mediated via an intermolecular contact. It illustrates how the structure of a protein can be modified by crystal contacts. Copyright 2000 Academic Press.

Simulation study of the initial crystallization processes of poly(3-hexylthiophene) in solution: ordering dynamics of main chains and side chains.

PubMed

Takizawa, Yuumi; Shimomura, Takeshi; Miura, Toshiaki

2013-05-23

We study the initial nucleation dynamics of poly(3-hexylthiophene) (P3HT) in solution, focusing on the relationship between the ordering process of main chains and that of side chains. We carried out Langevin dynamics simulation and found that the initial nucleation processes consist of three steps: the ordering of ring orientation, the ordering of main-chain vectors, and the ordering of side chains. At the start, the normal vectors of thiophene rings aligned in a very short time, followed by alignment of main-chain end-to-end vectors. The flexible side-chain ordering took almost 5 times longer than the rigid-main-chain ordering. The simulation results indicated that the ordering of side chains was induced after the formation of the regular stack structure of main chains. This slow ordering dynamics of flexible side chains is one of the factors that cause anisotropic nuclei growth, which would be closely related to the formation of nanofiber structures without external flow field. Our simulation results revealed how the combined structure of the planar and rigid-main-chain backbones and the sparse flexible side chains lead to specific ordering behaviors that are not observed in ordinary linear polymer crystallization processes.

Contribution of cutinase serine 42 side chain to the stabilization of the oxyanion transition state.

PubMed

Nicolas, A; Egmond, M; Verrips, C T; de Vlieg, J; Longhi, S; Cambillau, C; Martinez, C

1996-01-16

Cutinase from the fungus Fusarium solani pisi is a lipolytic enzyme able to hydrolyze both aggregated and soluble substrates. It therefore provides a powerful tool for probing the mechanisms underlying lipid hydrolysis. Lipolytic enzymes have a catalytic machinery similar to those present in serine proteinases. It is characterized by the triad Ser, His, and Asp (Glu) residues, by an oxyanion binding site that stabilizes the transition state via hydrogen bonds with two main chain amide groups, and possibly by other determinants. It has been suggested on the basis of a covalently bond inhibitor that the cutinase oxyanion hole may consist not only of two main chain amide groups but also of the Ser42 O gamma side chain. Among the esterases and the serine and the cysteine proteases, only Streptomyces scabies esterase, subtilisin, and papain, respectively, have a side chain residue which is involved in the oxyanion hole formation. The position of the cutinase Ser42 side chain is structurally conserved in Rhizomucor miehei lipase with Ser82 O gamma, in Rhizopus delemar lipase with Thr83 O gamma 1, and in Candida antartica B lipase with Thr40 O gamma 1. To evaluate the increase in the tetrahedral intermediate stability provided by Ser42 O gamma, we mutated Ser42 into Ala. Furthermore, since the proper orientation of Ser42 O gamma is directed by Asn84, we mutated Asn84 into Ala, Leu, Asp, and Trp, respectively, to investigate the contribution of this indirect interaction to the stabilization of the oxyanion hole. The S42A mutation resulted in a drastic decrease in the activity (450-fold) without significantly perturbing the three-dimensional structure. The N84A and N84L mutations had milder kinetic effects and did not disrupt the structure of the active site, whereas the N84W and N84D mutations abolished the enzymatic activity due to drastic steric and electrostatic effects, respectively.

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

On the relationship between NMR-derived amide order parameters and protein backbone entropy changes

PubMed Central

Sharp, Kim A.; O’Brien, Evan; Kasinath, Vignesh; Wand, A. Joshua

2015-01-01

Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O2NH) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O2NH < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O2axis. A calibration curve for backbone entropy vs. O2NH is developed which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O2NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, e.g. upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O2axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. PMID:25739366

On the relationship between NMR-derived amide order parameters and protein backbone entropy changes.

PubMed

Sharp, Kim A; O'Brien, Evan; Kasinath, Vignesh; Wand, A Joshua

2015-05-01

Molecular dynamics simulations are used to analyze the relationship between NMR-derived squared generalized order parameters of amide NH groups and backbone entropy. Amide order parameters (O(2) NH ) are largely determined by the secondary structure and average values appear unrelated to the overall flexibility of the protein. However, analysis of the more flexible subset (O(2) NH  < 0.8) shows that these report both on the local flexibility of the protein and on a different component of the conformational entropy than that reported by the side chain methyl axis order parameters, O(2) axis . A calibration curve for backbone entropy vs. O(2) NH is developed, which accounts for both correlations between amide group motions of different residues, and correlations between backbone and side chain motions. This calibration curve can be used with experimental values of O(2) NH changes obtained by NMR relaxation measurements to extract backbone entropy changes, for example, upon ligand binding. In conjunction with our previous calibration for side chain entropy derived from measured O(2) axis values this provides a prescription for determination of the total protein conformational entropy changes from NMR relaxation measurements. © 2015 Wiley Periodicals, Inc.

Switching effect of the side chain on quantum walks on triple graphs

NASA Astrophysics Data System (ADS)

Du, Yi-Mu; Lu, Li-Hua; Li, You-Quan

2015-07-01

We consider a continuous-time quantum walk on a triple graph and investigate the influence of the side chain on propagation in the main chain. Calculating the interchange of the probabilities between the two parts of the main chain, we find that a switching effect appears if there is an odd number of points in the side chain when concrete conditions between the length of the main chain and the position of the side chain are satisfied. However, such an effect does not occur if there is an even number of points in the side chain. We also suggest two proposals for experiments to demonstrate this effect, which may be employed to design a new type of switching device.

Adsorption of amino acids by fullerenes and fullerene nanowhiskers

NASA Astrophysics Data System (ADS)

Hashizume, Hideo; Hirata, Chika; Fujii, Kazuko; Miyazawa, Kun'ichi

2015-12-01

We have investigated the adsorption of some amino acids and an oligopeptide by fullerene (C60) and fullerene nanowhiskers (FNWs). C60 and FNWs hardly adsorbed amino acids. Most of the amino acids used have a hydrophobic side chain. Ala and Val, with an alkyl chain, were not adsorbed by the C60 or FNWs. Trp, Phe and Pro, with a cyclic structure, were not adsorbed by them either. The aromatic group of C60 did not interact with the side chain. The carboxyl or amino group, with the frame structure of an amino acid, has a positive or negative charge in solution. It is likely that the C60 and FNWs would not prefer the charged carboxyl or amino group. Tri-Ala was adsorbed slightly by the C60 and FNWs. The carboxyl or amino group is not close to the center of the methyl group of Tri-Ala. One of the methyl groups in Tri-Ala would interact with the aromatic structure of the C60 and FNWs. We compared our results with the theoretical interaction of 20 bio-amino acids with C60. The theoretical simulations showed the bonding distance between C60 and an amino acid and the dissociation energy. The dissociation energy was shown to increase in the order, Val < Phe < Pro < Asp < Ala < Trp < Tyr < Arg < Leu. However, the simulation was not consistent with our experimental results. The adsorption of albumin (a protein) by C60 showed the effect on the side chains of Try and Trp. The structure of albumin was changed a little by C60. In our study Try and Tyr were hardly adsorbed by C60 and FNWs. These amino acids did not show a different adsorption behavior compared with other amino acids. The adsorptive behavior of mono-amino acids might be different from that of polypeptides.

Protein side chain conformation predictions with an MMGBSA energy function.

PubMed

Gaillard, Thomas; Panel, Nicolas; Simonson, Thomas

2016-06-01

The prediction of protein side chain conformations from backbone coordinates is an important task in structural biology, with applications in structure prediction and protein design. It is a difficult problem due to its combinatorial nature. We study the performance of an "MMGBSA" energy function, implemented in our protein design program Proteus, which combines molecular mechanics terms, a Generalized Born and Surface Area (GBSA) solvent model, with approximations that make the model pairwise additive. Proteus is not a competitor to specialized side chain prediction programs due to its cost, but it allows protein design applications, where side chain prediction is an important step and MMGBSA an effective energy model. We predict the side chain conformations for 18 proteins. The side chains are first predicted individually, with the rest of the protein in its crystallographic conformation. Next, all side chains are predicted together. The contributions of individual energy terms are evaluated and various parameterizations are compared. We find that the GB and SA terms, with an appropriate choice of the dielectric constant and surface energy coefficients, are beneficial for single side chain predictions. For the prediction of all side chains, however, errors due to the pairwise additive approximation overcome the improvement brought by these terms. We also show the crucial contribution of side chain minimization to alleviate the rigid rotamer approximation. Even without GB and SA terms, we obtain accuracies comparable to SCWRL4, a specialized side chain prediction program. In particular, we obtain a better RMSD than SCWRL4 for core residues (at a higher cost), despite our simpler rotamer library. Proteins 2016; 84:803-819. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Protein Side-Chain Resonance Assignment and NOE Assignment Using RDC-Defined Backbones without TOCSY Data3

PubMed Central

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

2011-01-01

One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA have backbone RMSD 0.8 – 1.5 Å from the reference structures determined by traditional NMR approaches. PMID:21706248

Use of side-chain for rational design of n-type diketopyrrolopyrrole-based conjugated polymers: what did we find out?

PubMed

Kanimozhi, Catherine; Yaacobi-Gross, Nir; Burnett, Edmund K; Briseno, Alejandro L; Anthopoulos, Thomas D; Salzner, Ulrike; Patil, Satish

2014-08-28

The primary role of substituted side chains in organic semiconductors is to increase their solubility in common organic solvents. In the recent past, many literature reports have suggested that the side chains play a critical role in molecular packing and strongly impact the charge transport properties of conjugated polymers. In this work, we have investigated the influence of side-chains on the charge transport behavior of a novel class of diketopyrrolopyrrole (DPP) based alternating copolymers. To investigate the role of side-chains, we prepared four diketopyrrolopyrrole-diketopyrrolopyrrole (DPP-DPP) conjugated polymers with varied side-chains and carried out a systematic study of thin film microstructure and charge transport properties in polymer thin-film transistors (PTFTs). Combining results obtained from grazing incidence X-ray diffraction (GIXD) and charge transport properties in PTFTs, we conclude side-chains have a strong influence on molecular packing, thin film microstructure, and the charge carrier mobility of DPP-DPP copolymers. However, the influence of side-chains on optical properties was moderate. The preferential "edge-on" packing and dominant n-channel behavior with exceptionally high field-effect electron mobility values of >1 cm(2) V(-1) s(-1) were observed by incorporating hydrophilic (triethylene glycol) and hydrophobic side-chains of alternate DPP units. In contrast, moderate electron and hole mobilities were observed by incorporation of branched hydrophobic side-chains. This work clearly demonstrates that the subtle balance between hydrophobicity and hydrophilicity induced by side-chains is a powerful strategy to alter the molecular packing and improve the ambipolar charge transport properties in DPP-DPP based conjugated polymers. Theoretical analysis supports the conclusion that the side-chains influence polymer properties through morphology changes, as there is no effect on the electronic properties in the gas phase. The exceptional electron mobility is at least partially a result of the strong intramolecular conjugation of the donor and acceptor as evidenced by the unusually wide conduction band of the polymer.

TSAR, a new graph-theoretical approach to computational modeling of protein side-chain flexibility: modeling of ionization properties of proteins.

PubMed

Stroganov, Oleg V; Novikov, Fedor N; Zeifman, Alexey A; Stroylov, Viktor S; Chilov, Ghermes G

2011-09-01

A new graph-theoretical approach called thermodynamic sampling of amino acid residues (TSAR) has been elaborated to explicitly account for the protein side chain flexibility in modeling conformation-dependent protein properties. In TSAR, a protein is viewed as a graph whose nodes correspond to structurally independent groups and whose edges connect the interacting groups. Each node has its set of states describing conformation and ionization of the group, and each edge is assigned an array of pairwise interaction potentials between the adjacent groups. By treating the obtained graph as a belief-network-a well-established mathematical abstraction-the partition function of each node is found. In the current work we used TSAR to calculate partition functions of the ionized forms of protein residues. A simplified version of a semi-empirical molecular mechanical scoring function, borrowed from our Lead Finder docking software, was used for energy calculations. The accuracy of the resulting model was validated on a set of 486 experimentally determined pK(a) values of protein residues. The average correlation coefficient (R) between calculated and experimental pK(a) values was 0.80, ranging from 0.95 (for Tyr) to 0.61 (for Lys). It appeared that the hydrogen bond interactions and the exhaustiveness of side chain sampling made the most significant contribution to the accuracy of pK(a) calculations. Copyright © 2011 Wiley-Liss, Inc.

Functionalization of magnetic nanocrystals by oligo (ethylene oxide) chains carrying diazonium and iniferter end groups.

PubMed

Ahmad, Randa; Griffete, Nébéwia; Lamouri, Aazdine; Mangeney, Claire

2013-10-01

The water stability of iron oxide nanoparticles (NPs) is a major issue for biomedical and biological applications. This paper presents a versatile approach for preparing water-soluble iron oxide nanoparticles coated by bifunctional oligo(ethylene oxide) (OEO) chains, carrying on the one side a diazonium end group for covalent grafting at the NP surface and on the other side an iniferter group (diethyl dithiocarbamate) for initiating the growing of poly(methacrylic acid). The nanoparticles were synthesized by coprecipitation in basic media and functionalized in situ by adding the diazonium salt directly in the synthesis medium. Oligo(ethylene oxide) with various chain lengths (from one to three monomer units) was grafted at the NP surface using this approach. The length of the OEO spacer between the NP surface and the iniferter end group was found to be a critical parameter for controlling the colloidal stability of the hybrid NPs. The polymerization time was also shown to strongly influence their colloidal stability, emphasizing the interest to control the interfacial properties of the hybrids for obtaining stable dispersions in water. Copyright © 2013 Elsevier Inc. All rights reserved.

Influence of Trp flipping on carbohydrate binding in lectins. An example on Aleuria aurantia lectin AAL.

PubMed

Houser, Josef; Kozmon, Stanislav; Mishra, Deepti; Mishra, Sushil K; Romano, Patrick R; Wimmerová, Michaela; Koča, Jaroslav

2017-01-01

Protein-carbohydrate interactions are very often mediated by the stacking CH-π interactions involving the side chains of aromatic amino acids such as tryptophan (Trp), tyrosine (Tyr) or phenylalanine (Phe). Especially suitable for stacking is the Trp residue. Analysis of the PDB database shows Trp stacking for 265 carbohydrate or carbohydrate like ligands in 5 208 Trp containing motives. An appropriate model system to study such an interaction is the AAL lectin family where the stacking interactions play a crucial role and are thought to be a driving force for carbohydrate binding. In this study we present data showing a novel finding in the stacking interaction of the AAL Trp side chain with the carbohydrate. High resolution X-ray structure of the AAL lectin from Aleuria aurantia with α-methyl-l-fucoside ligand shows two possible Trp side chain conformations with the same occupation in electron density. The in silico data shows that the conformation of the Trp side chain does not influence the interaction energy despite the fact that each conformation creates interactions with different carbohydrate CH groups. Moreover, the PDB data search shows that the conformations are almost equally distributed across all Trp-carbohydrate complexes, which would suggest no substantial preference for one conformation over another.

Energetically Unfavorable Amide Conformations for N6-Acetyllysine Side Chains in Refined Protein Structures

PubMed Central

Genshaft, Alexander; Moser, Joe-Ann S.; D'Antonio, Edward L.; Bowman, Christine M.; Christianson, David W.

2013-01-01

The reversible acetylation of lysine to form N6-acetyllysine in the regulation of protein function is a hallmark of epigenetics. Acetylation of the positively charged amino group of the lysine side chain generates a neutral N-alkylacetamide moiety that serves as a molecular “switch” for the modulation of protein function and protein-protein interactions. We now report the analysis of 381 N6-acetyllysine side chain amide conformations as found in 79 protein crystal structures and 11 protein NMR structures deposited in the Protein Data Bank (PDB) of the Research Collaboratory for Structural Bioinformatics. We find that only 74.3% of N6-acetyllysine residues in protein crystal structures and 46.5% in protein NMR structures contain amide groups with energetically preferred trans or generously trans conformations. Surprisingly, 17.6% of N6-acetyllysine residues in protein crystal structures and 5.3% in protein NMR structures contain amide groups with energetically unfavorable cis or generously cis conformations. Even more surprisingly, 8.1% of N6-acetyllysine residues in protein crystal structures and 48.2% in NMR structures contain amide groups with energetically prohibitive twisted conformations that approach the transition state structure for cis-trans isomerization. In contrast, 109 unique N-alkylacetamide groups contained in 84 highly-accurate small molecule crystal structures retrieved from the Cambridge Structural Database exclusively adopt energetically preferred trans conformations. Therefore, we conclude that cis and twisted N6-acetyllysine amides in protein structures deposited in the PDB are erroneously modeled due to their energetically unfavorable or prohibitive conformations. PMID:23401043

Biopolymers Containing Unnatural Amino Acids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Peter

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

Mutation of Phe413 to Tyr in catalase KatE from Escherichia coli leads to side chain damage and main chain cleavage.

PubMed

Jha, Vikash; Donald, Lynda J; Loewen, Peter C

2012-09-15

The monofunctional catalase KatE of Esherichia coli exhibits exceptional resistance to heat denaturation and proteolytic degradation. During an investigation of subtle conformation changes in Arg111 and Phe413 on the proximal side of the heme induced by H(2)O(2), variants at position R111, T115 and F413 were constructed. Because the residues are not situated in the distal side heme cavity where catalysis occurs, significant changes in reactivity were not expected and indeed, only small changes in the kinetic characteristics were observed in all of the variants. However, the F413Y variant was found to have undergone main chain cleavage whereas the R111A, T115A, F413E and F413K variants had not. Two sites of cleavage were identified in the crystal structure and by mass spectrometry at residues 111 and 115. In addition to main chain cleavage, modifications to the side chains of Tyr413, Thr115 and Arg111 were suggested by differences in the electron density maps compared to maps of the native and inactive variant H128N/F413Y. The inactive variant H128N/F413Y and the active variant T115A/F413Y both did not exhibit main chain cleavage and the R11A/F413Y variant exhibited less cleavage. In addition, the apparent modification of three side chains was largely absent in these variants. It is also significant that all three F413 single variants contained heme b suggesting that the fidelity of the phenyl group was important for mediating heme b oxidation to heme d. The reactions are attributed to the introduction of a new reactive center possibly involving a transient radical on Tyr413 formed during catalytic turn over. Copyright © 2011 Elsevier Inc. All rights reserved.

Biopolymers Containing Unnatural Building Blocks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Peter G.

2013-06-30

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

Antimocrobial Polymer

DOEpatents

McDonald, William F.; Huang, Zhi-Heng; Wright, Stacy C.

2005-09-06

A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from quaternary ammonium compounds, gentian violet compounds, substituted or unsubstituted phenols, biguanide compounds, iodine compounds, and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A)3P wherein A is hydroxyalkyl; and the antimicrobial agent is chlorhexidine, dimethylchlorophenol, cetyl pyridinium chloride, gentian violet, triclosan, thymol, iodine, and mixtures thereof.

Antimicrobial Polymer

DOEpatents

McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

2004-09-28

A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

Automated side-chain model building and sequence assignment by template matching.

PubMed

Terwilliger, Thomas C

2003-01-01

An algorithm is described for automated building of side chains in an electron-density map once a main-chain model is built and for alignment of the protein sequence to the map. The procedure is based on a comparison of electron density at the expected side-chain positions with electron-density templates. The templates are constructed from average amino-acid side-chain densities in 574 refined protein structures. For each contiguous segment of main chain, a matrix with entries corresponding to an estimate of the probability that each of the 20 amino acids is located at each position of the main-chain model is obtained. The probability that this segment corresponds to each possible alignment with the sequence of the protein is estimated using a Bayesian approach and high-confidence matches are kept. Once side-chain identities are determined, the most probable rotamer for each side chain is built into the model. The automated procedure has been implemented in the RESOLVE software. Combined with automated main-chain model building, the procedure produces a preliminary model suitable for refinement and extension by an experienced crystallographer.

Protein-ligand docking with multiple flexible side chains

NASA Astrophysics Data System (ADS)

Zhao, Yong; Sanner, Michel F.

2008-09-01

In this work, we validate and analyze the results of previously published cross docking experiments and classify failed dockings based on the conformational changes observed in the receptors. We show that a majority of failed experiments (i.e. 25 out of 33, involving four different receptors: cAPK, CDK2, Ricin and HIVp) are due to conformational changes in side chains near the active site. For these cases, we identify the side chains to be made flexible during docking calculation by superimposing receptors and analyzing steric overlap between various ligands and receptor side chains. We demonstrate that allowing these side chains to assume rotameric conformations enables the successful cross docking of 19 complexes (ligand all atom RMSD < 2.0 Å) using our docking software FLIPDock. The number of side receptor side chains interacting with a ligand can vary according to the ligand's size and shape. Hence, when starting from a complex with a particular ligand one might have to extend the region of potential interacting side chains beyond the ones interacting with the known ligand. We discuss distance-based methods for selecting additional side chains in the neighborhood of the known active site. We show that while using the molecular surface to grow the neighborhood is more efficient than Euclidian-distance selection, the number of side chains selected by these methods often remains too large and additional methods for reducing their count are needed. Despite these difficulties, using geometric constraints obtained from the network of bonded and non-bonded interactions to rank residues and allowing the top ranked side chains to be flexible during docking makes 22 out of 25 complexes successful.

Asymmetric Alkyl Side-Chain Engineering of Naphthalene Diimide-Based n-Type Polymers for Efficient All-Polymer Solar Cells.

PubMed

Jia, Tao; Li, Zhenye; Ying, Lei; Jia, Jianchao; Fan, Baobing; Zhong, Wenkai; Pan, Feilong; He, Penghui; Chen, Junwu; Huang, Fei; Cao, Yong

2018-02-13

The design and synthesis of three n-type conjugated polymers based on a naphthalene diimide-thiophene skeleton are presented. The control polymer, PNDI-2HD, has two identical 2-hexyldecyl side chains, and the other polymers have different alkyl side chains; PNDI-EHDT has a 2-ethylhexyl and a 2-decyltetradecyl side chain, and PNDI-BOOD has a 2-butyloctyl and a 2-octyldodecyl side chain. These copolymers with different alkyl side chains exhibit higher melting and crystallization temperatures, and stronger aggregation in solution, than the control copolymer PNDI-2HD that has the same side chain. Polymer solar cells based on the electron-donating copolymer PTB7-Th and these novel copolymers exhibit nearly the same open-circuit voltage of 0.77 V. Devices based on the copolymer PNDI-BOOD with different side chains have a power-conversion efficiency of up to 6.89%, which is much higher than the 4.30% obtained with the symmetric PNDI-2HD. This improvement can be attributed to the improved charge-carrier mobility and the formation of favorable film morphology. These observations suggest that the molecular design strategy of incorporating different side chains can provide a new and promising approach to developing n-type conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains.

PubMed

Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A

2017-01-19

The physics-based potentials of side-chain-side-chain interactions corresponding to pairs composed of charged and polar, polar and polar, charged and hydrophobic, and hydrophobic and hydrophobic side chains have been determined. A total of 144 four-dimensional potentials of mean force (PMFs) of all possible pairs of molecules modeling these pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expressions were then fitted to the PMFs. Depending on the type of interacting sites, the analytical approximation to the PMF is a sum of terms corresponding to van der Waals interactions and cavity-creation involving the nonpolar sections of the side chains and van der Waals, cavity-creation, and electrostatic (charge-dipole or dipole-dipole) interaction energies and polarization energies involving the charged or polar sections of the side chains. The model used in this work reproduces all features of the interacting pairs. The UNited RESidue force field with the new side-chain-side-chain interaction potentials was preliminarily tested with the N-terminal part of the B-domain of staphylococcal protein A (PDBL 1BDD ; a three-α-helix bundle) and UPF0291 protein YnzC from Bacillus subtilis (PDB: 2HEP ; an α-helical hairpin).

C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.

PubMed

Higgins, Chelsea D; Koellhoffer, Jayne F; Chandran, Kartik; Lai, Jonathan R

2013-10-01

We previously described potent inhibition of Ebola virus entry by a 'C-peptide' based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo'). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain crosslinks to promote α-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~10(3)-fold reduction in infection at 40 μM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain-side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong α-helical conformation that was independent of concentration. Side chain-side chain crosslinking enhanced α-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Factors affecting the use of 13Cα chemical shifts to determine, refine, and validate protein structures

PubMed Central

Vila, Jorge A.; Scheraga, Harold A.

2008-01-01

Interest centers here on the analysis of two different, but related, phenomena that affect side-chain conformations and consequently 13Cα chemical shifts and their applications to determine, refine, and validate protein structures. The first is whether 13Cα chemical shifts, computed at the DFT level of approximation with charged residues is a better approximation of observed 13Cα chemical shifts than those computed with neutral residues for proteins in solution. Accurate computation of 13Cα chemical shifts requires a proper representation of the charges, which might not take on integral values. For this analysis, the charges for 139 conformations of the protein ubiquitin were determined by explicit consideration of protein binding equilibria, at a given pH, that is, by exploring the 2ξ possible ionization states of the whole molecule, with ξ being the number of ionizable groups. The results of this analysis, as revealed by the shielding/deshield-ing of the 13Cα nucleus, indicated that: (i) there is a significant difference in the computed 13Cα chemical shifts, between basic and acidic groups, as a function of the degree of charge of the side chain; (ii) this difference is attributed to the distance between the ionizable groups and the 13Cα nucleus, which is shorter for the acidic Asp and Glu groups as compared with that for the basic Lys and Arg groups; and (iii) the use of neutral, rather than charged, basic and acidic groups is a better approximation of the observed 13Cα chemical shifts of a protein in solution. The second is how side-chain flexibility influences computed 13Cα chemical shifts in an additional set of ubiquitin conformations, in which the side chains are generated from an NMR-derived structure with the backbone conformation assumed to be fixed. The 13Cα chemical shift of a given amino acid residue in a protein is determined, mainly, by its own backbone and side-chain torsional angles, independent of the neighboring residues; the conformation of a given residue itself, however, depends on the environment of this residue and, hence, on the whole protein structure. As a consequence, this analysis reveals the role and impact of an accurate side-chain computation in the determination and refinement of protein conformation. The results of this analysis are: (i) a lower error between computed and observed 13Cα chemical shifts (by up to 3.7 ppm), was found for ~68% and ~63% of all ionizable residues and all non-Ala/Pro/Gly residues, respectively, in the additional set of conformations, compared with results for the model from which the set was derived; and (ii) all the additional conformations exhibit a lower root-mean-square-deviation (1.97 ppm ≤ rmsd ≤ 2.13 ppm), between computed and observed 13Cα chemical shifts, than the rmsd (2.32 ppm) computed for the starting conformation from which this additional set was derived. As a validation test, an analysis of the additional set of ubiquitin conformations, comparing computed and observed values of both 13Cα chemical shifts and χ1 torsional angles (given by the vicinal coupling constants, 3JN–Cγ and 3JC′–Cγ, is discussed. PMID:17975838

Effects of Alkylthio and Alkoxy Side Chains in Polymer Donor Materials for Organic Solar Cells.

PubMed

Cui, Chaohua; Wong, Wai-Yeung

2016-02-01

Side chains play a considerable role not only in improving the solubility of polymers for solution-processed device fabrication, but also in affecting the molecular packing, electron affinity and thus the device performance. In particular, electron-donating side chains show unique properties when employed to tune the electronic character of conjugated polymers in many cases. Therefore, rational electron-donating side chain engineering can improve the photovoltaic properties of the resulting polymer donors to some extent. Here, a survey of some representative examples which use electron-donating alkylthio and alkoxy side chains in conjugated organic polymers for polymer solar cell applications will be presented. It is envisioned that an analysis of the effect of such electron-donating side chains in polymer donors would contribute to a better understanding of this kind of side chain behavior in solution-processed conjugated organic polymers for polymer solar cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-Function of the Cytochrome b 6f Complex of Oxygenic Photosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cramer, W. A.; Yamashita, E.; Baniulis, D.

2014-03-20

Structure–function of the major integral membrane cytochrome b 6f complex that functions in cyanobacteria, algae, and green plants to transfer electrons between the two reaction center complexes in the electron transport chain of oxygenic photosynthesis is discussed in the context of recently obtained crystal structures of the complex and soluble domains of cytochrome f and the Rieske iron–sulfur protein. The energy-transducing function of the complex, generation of the proton trans-membrane electrochemical potential gradient, centers on the oxidation/reduction pathways of the plastoquinol/plastoquinone (QH 2/Q), the proton donor/acceptor within the complex. These redox reactions are carried out by five redox prosthetic groupsmore » embedded in each monomer, the high potential two iron–two sulfur cluster and the heme of cytochrome f on the electropositive side (p) of the complex, two noncovalently bound b-type hemes that cross the complex and the membrane, and a covalently bound c-type heme (c n) on the electronegative side (n). These five redox-active groups are organized in high- (cyt f/[2Fe–2S] and low-potential (hemes b p, b n, c n) electron transport pathways that oxidize and reduce the quinol and quinone on the p- and n-sides in a Q-cycle-type mechanism, while translocating as many as 2 H + to the p-side aqueous side for every electron transferred through the high potential chain to the photosystem I reaction center. The presence of heme c n and the connection of the n-side of the membrane and b 6f complex to the cyclic electron transport chain indicate that the Q cycle in the oxygenic photosynthetic electron transport chain differs from those connected to the bc 1 complex in the mitochondrial respiratory chain and the chain in photosynthetic bacteria. Inferences from the structure and C2 symmetry of the complex for the pathway of QH 2/Q transfer within the complex, problems posed by the presence of lipid in the inter-monomer cavity, and the narrow portal for QH2 passage through the p-side oxidation site proximal to the [2Fe–2S] cluster are discussed.« less

Fourier transform microwave spectroscopy of Ac-Ser-NH2: the role of side chain interactions in peptide folding.

PubMed

Cabezas, Carlos; Robben, Martinus A T; Rijs, Anouk M; Peña, Isabel; Alonso, J L

2015-08-21

Serine capped dipeptide N-acetyl-l-serinamide (Ac-Ser-NH2) has been investigated using Fourier transform microwave spectroscopic techniques combined with laser ablation sources. Spectral signatures originating from one dominant species have been detected in the supersonic expansion. Rotational and nuclear quadrupole coupling constants of the two (14)N nuclei have been used in the characterization of a C/γ-turn structure, which is stabilized by a CO∙∙∙HN intramolecular hydrogen bond closing a seven-membered ring. Two extra hydrogen bonds involving the polar side chain (-CH2OH) further stabilize the structure. The non-observation of C5 species, attributed to the presence of the polar side chain, is in contrast with the previous gas phase observation of the related dipeptides containing glycine or alanine residues. The A-E splitting pattern arising from the internal rotation of the methyl group has been analyzed and the internal rotation barrier has been determined.

Application of 2-chlorotrityl resin in solid phase synthesis of (Leu15)-gastrin I and unsulfated cholecystokinin octapeptide. Selective O-deprotection of tyrosine.

PubMed

Barlos, K; Gatos, D; Kapolos, S; Poulos, C; Schäfer, W; Yao, W Q

1991-12-01

The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH2, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu15)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloromethane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide.

MCCE2: improving protein pKa calculations with extensive side chain rotamer sampling.

PubMed

Song, Yifan; Mao, Junjun; Gunner, M R

2009-11-15

Multiconformation continuum electrostatics (MCCE) explores different conformational degrees of freedom in Monte Carlo calculations of protein residue and ligand pK(a)s. Explicit changes in side chain conformations throughout a titration create a position dependent, heterogeneous dielectric response giving a more accurate picture of coupled ionization and position changes. The MCCE2 methods for choosing a group of input heavy atom and proton positions are described. The pK(a)s calculated with different isosteric conformers, heavy atom rotamers and proton positions, with different degrees of optimization are tested against a curated group of 305 experimental pK(a)s in 33 proteins. QUICK calculations, with rotation around Asn and Gln termini, sampling His tautomers and torsion minimum hydroxyls yield an RMSD of 1.34 with 84% of the errors being <1.5 pH units. FULL calculations adding heavy atom rotamers and side chain optimization yield an RMSD of 0.90 with 90% of the errors <1.5 pH unit. Good results are also found for pK(a)s in the membrane protein bacteriorhodopsin. The inclusion of extra side chain positions distorts the dielectric boundary and also biases the calculated pK(a)s by creating more neutral than ionized conformers. Methods for correcting these errors are introduced. Calculations are compared with multiple X-ray and NMR derived structures in 36 soluble proteins. Calculations with X-ray structures give significantly better pK(a)s. Results with the default protein dielectric constant of 4 are as good as those using a value of 8. The MCCE2 program can be downloaded from http://www.sci.ccny.cuny.edu/~mcce. 2009 Wiley Periodicals, Inc.

Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.

PubMed

Pan, Lucy Yan; Salas-Solano, Oscar; Valliere-Douglass, John F

Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in C H 2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.

Concepts for the material development of phosphorescent organic materials processable from solution and their application in OLEDs

NASA Astrophysics Data System (ADS)

Janietz, S.; Krueger, H.; Thesen, M.; Salert, B.; Wedel, A.

2014-10-01

One example of organic electronics is the application of polymer based light emitting devices (PLEDs). PLEDs are very attractive for large area and fine-pixel displays, lighting and signage. The polymers are more amenable to solution processing by printing techniques which are favourable for low cost production in large areas. With phosphorescent emitters like Ir-complexes higher quantum efficiencies were obtained than with fluorescent systems, especially if multilayer stack systems with separated charge transport and emitting layers were applied in the case of small molecules. Polymers exhibit the ability to integrate all the active components like the hole-, electron-transport and phosphorescent molecules in only one layer. Here, the active components of a phosphorescent system - triplet emitter, hole- and electron transport molecules - can be linked as a side group to a polystyrene main chain. By varying the molecular structures of the side groups as well as the composition of the side chains with respect to the triplet emitter, hole- and electron transport structure, and by blending with suitable glass-forming, so-called small molecules, brightness, efficiency and lifetime of the produced OLEDs can be optimized. By choosing the triplet emitter, such as iridium complexes, different emission colors can be specially set. Different substituted triazine molecules were introduced as side chain into a polystyrene backbone and applied as electron transport material in PLED blend systems. The influence of alkyl chain lengths of the performance will be discussed. For an optimized blend system with a green emitting phosphorescent Ir-complex efficiencies of 60 cd/A and an lifetime improvement of 66.000 h @ 1000 cd/m2 were achieved.

Alpha-helix to beta-sheet transition in long-chain poly-l-lysine: Formation of alpha-helical fibrils by poly-l-lysine.

PubMed

Cieślik-Boczula, Katarzyna

2017-06-01

The temperature-induced α-helix to β-sheet transition in long-chain poly-l-lysine (PLL), accompanied by the gauche-to-trans isomerization of CH 2 groups in the hydrocarbon side chains of Lys amino acid residues, and formation of β-sheet as well as α-helix fibrillar aggregates of PLL have been studied using Fourier-transform infrared (FT-IR) and vibrational circular dichroism (VCD) spectroscopy, and transmission electron microscopy (TEM). In a low-temperature alkaline water solution or in a methanol-rich water mixture, the secondary structure of PLL is represented by α-helical conformations with unordered and gauche-rich hydrocarbon side chains. Under these conditions, PLL molecules aggregate into α-helical fibrils. PLLs dominated by extended antiparallel β-sheet structures with highly ordered trans-rich hydrocarbon side chains are formed in a high-temperature range at alkaline pD and aggregate into fibrillar, protofibrillar, and spherical forms. Presented data support the idea that fibrillar aggregation is a varied phenomenon possible in repetitive structural elements with not only a β-sheet-rich conformation, but also an α-helical-rich conformation. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Hidden regularity and universal classification of fast side chain motions in proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajeshwar, Rajitha; Smith, Jeremy C.; Krishnam, Marimuthu

Proteins display characteristic dynamical signatures that appear to be universal across all proteins regardless of topology and size. Here, we systematically characterize the universal features of fast side chain motions in proteins by examining the conformational energy surfaces of individual residues obtained using enhanced sampling molecular dynamics simulation (618 free energy surfaces obtained from 0.94 s MD simulation). The side chain conformational free energy surfaces obtained using the adaptive biasing force (ABF) method for a set of eight proteins with different molecular weights and secondary structures are used to determine the methyl axial NMR order parameters (O axis 2), populationsmore » of side chain rotamer states (ρ), conformational entropies (S conf), probability fluxes, and activation energies for side chain inter-rotameric transitions. The free energy barriers separating side chain rotamer states range from 0.3 to 12 kcal/mol in all proteins and follow a trimodal distribution with an intense peak at ~5 kcal/mol and two shoulders at ~3 and ~7.5 kcal/mol, indicating that some barriers are more favored than others by proteins to maintain a balance between their conformational stability and flexibility. The origin and the influences of the trimodal barrier distribution on the distribution of O axis 2 and the side chain conformational entropy are discussed. A hierarchical grading of rotamer states based on the conformational free energy barriers, entropy, and probability flux reveals three distinct classes of side chains in proteins. A unique nonlinear correlation is established between O axis 2 and the side chain rotamer populations (ρ). In conclusion, the apparent universality in O axis 2 versus correlation, trimodal barrier distribution, and distinct characteristics of three classes of side chains observed among all proteins indicates a hidden regularity (or commonality) in the dynamical heterogeneity of fast side chain motions in proteins.« less

Recovery and fine structure variability of RGII sub-domains in wine (Vitis vinifera Merlot)

PubMed Central

Buffetto, F.; Ropartz, D.; Zhang, X. J.; Gilbert, H. J.; Guillon, F.; Ralet, M.-C.

2014-01-01

Background and Aims Rhamnogalacturonan II (RGII) is a structurally complex pectic sub-domain composed of more than 12 different sugars and 20 different linkages distributed in five side chains along a homogalacturonan backbone. Although RGII has long been described as highly conserved over plant evolution, recent studies have revealed variations in the structure of the polysaccharide. This study examines the fine structure variability of RGII in wine, focusing on the side chains A and B obtained after sequential mild acid hydrolysis. Specifically, this study aims to differentiate intrinsic structural variations in these RGII side chains from structural variations due to acid hydrolysis. Methods RGII from wine (Vitis vinifera Merlot) was sequentially hydrolysed with trifluoroacetic acid (TFA) and the hydrolysis products were separated by anion-exchange chromatography (AEC). AEC fractions or total hydrolysates were analysed by MALDI-TOF mass spectrometry. Key Results The optimal conditions to recover non-degraded side chain B, side chain A and RGII backbone were 0·1 m TFA at 40 °C for 16 h, 0·48 m TFA at 40 °C for 16 h (or 0·1 m TFA at 60 °C for 8 h) and 0·1 m TFA at 60 °C for 16 h, respectively. Side chain B was particularly prone to acid degradation. Side chain A and the RGII GalA backbone were partly degraded by 0·1 m TFA at 80 °C for 1–4 h. AEC allowed separation of side chain B, methyl-esterified side chain A and non-methyl-esterified side chain A. The structure of side chain A and the GalA backbone were highly variable. Conclusions Several modifications to the RGII structure of wine were identified. The observed dearabinosylation and deacetylation were primarily the consequence of acidic treatment, while variation in methyl-esterification, methyl-ether linkages and oxidation reflect natural diversity. The physiological significance of this variability, however, remains to be determined. PMID:24908680

Reorientation Motion and Preferential Interactions of a Peptide in Denaturants and Osmolyte.

PubMed

Jas, Gouri S; Rentchler, Eric C; Słowicka, Agnieszka M; Hermansen, John R; Johnson, Carey K; Middaugh, C Russell; Kuczera, Krzysztof

2016-03-31

Fluorescence anisotropy decay measurements and all atom molecular dynamics simulations are used to characterize the orientational motion and preferential interaction of a peptide, N-acetyl-tryptophan-amide (NATA) containing two peptide bonds, in aqueous, urea, guanidinium chloride (GdmCl), and proline solution. Anisotropy decay measurements as a function of temperature and concentration showed moderate slowing of reorientations in urea and GdmCl and very strong slowing in proline solution, relative to water. These effects deviate significantly from simple proportionality of peptide tumbling time to solvent viscosity, leading to the investigation of microscopic preferential interaction behavior through molecular dynamics simulations. Examination of the interactions of denaturants and osmolyte with the peptide backbone uncovers the presence of strongest interaction with urea, intermediate with proline, and weakest with GdmCl. In contrast, the strongest preferential solvation of the peptide side chain is by the nonpolar part of the proline zwitterion, followed by urea, and GdmCl. Interestingly, the local density of urea around the side chain is higher, but the GdmCl distribution is more organized. Thus, the computed preferential solvation of the side chain by the denaturants and osmolyte can account for the trend in reorientation rates. Analysis of water structure and its dynamics uncovered underlying differences between urea, GdmCl, and proline. Urea exerted the smallest perturbation of water behavior. GdmCl had a larger effect on water, slowing kinetics and stabilizing interactions. Proline had the largest overall interactions, exhibiting a strong stabilizing effect on both water-water and water-peptide hydrogen bonds. The results for this elementary peptide system demonstrate significant differences in microscopic behavior of the examined solvent environments. For the commonly used denaturants, urea tends to form disorganized local aggregates around the peptide groups and has little influence on water, while GdmCl only forms specific interactions with the side chain and tends to destabilize water structure. The protective osmolyte proline has the strongest and most specific interactions with the tryptophan side chain, and also stabilizes both water-water and water-peptide hydrogen bonds. Our results strongly suggest protein or peptide denaturation triggered by urea occurs by direct interaction, whereas GdmCl interacts favorably with side chains and destabilizes peptide-water hydrogen bonds. The stabilization of biopolymers by an osmolyte such as proline is governed by favorable preferential interaction with the side chains and stabilization of water.

Diketopyrrolopyrrole-based Conjugated Polymers Bearing Branched Oligo(Ethylene Glycol) Side Chains for Photovoltaic Devices.

PubMed

Chen, Xingxing; Zhang, Zijian; Ding, Zicheng; Liu, Jun; Wang, Lixiang

2016-08-22

Conjugated polymers are essential for solution-processable organic opto-electronic devices. In contrast to the great efforts on developing new conjugated polymer backbones, research on developing side chains is rare. Herein, we report branched oligo(ethylene glycol) (OEG) as side chains of conjugated polymers. Compared with typical alkyl side chains, branched OEG side chains endowed the resulting conjugated polymers with a smaller π-π stacking distance, higher hole mobility, smaller optical band gap, higher dielectric constant, and larger surface energy. Moreover, the conjugated polymers with branched OEG side chains exhibited outstanding photovoltaic performance in polymer solar cells. A power conversion efficiency of 5.37 % with near-infrared photoresponse was demonstrated and the device performance could be insensitive to the active layer thickness. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tuning the thermal conductivity of solar cell polymers through side chain engineering.

PubMed

Guo, Zhi; Lee, Doyun; Liu, Yi; Sun, Fangyuan; Sliwinski, Anna; Gao, Haifeng; Burns, Peter C; Huang, Libai; Luo, Tengfei

2014-05-07

Thermal transport is critical to the performance and reliability of polymer-based energy devices, ranging from solar cells to thermoelectrics. This work shows that the thermal conductivity of a low band gap conjugated polymer, poly(4,8-bis-alkyloxybenzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-(alkylthieno[3,4-b]thiophene-2-carboxylate)-2,6-diyl) (PBDTTT), for photovoltaic applications can be actively tuned through side chain engineering. Compared to the original polymer modified with short branched side chains, the engineered polymer using all linear and long side chains shows a 160% increase in thermal conductivity. The thermal conductivity of the polymer exhibits a good correlation with the side chain lengths as well as the crystallinity of the polymer characterized using small-angle X-ray scattering (SAXS) experiments. Molecular dynamics simulations and atomic force microscopy are used to further probe the molecular level local order of different polymers. It is found that the linear side chain modified polymer can facilitate the formation of more ordered structures, as compared to the branched side chain modified ones. The effective medium theory modelling also reveals that the long linear side chain enables a larger heat carrier propagation length and the crystalline phase in the bulk polymer increases the overall thermal conductivity. It is concluded that both the length of the side chains and the induced polymer crystallization are important for thermal transport. These results offer important guidance for actively tuning the thermal conductivity of conjugated polymers through molecular level design.

Room temperature structures and odd even behaviour of a homologous series of anhydrous lithium n-alkanoates

NASA Astrophysics Data System (ADS)

White, Nicole A. S.; Ellis, Henry A.

2008-10-01

The molecular structures of a homologous series of lithium n-alkanoates have been determined at room temperature using infrared spectroscopy, polarizing light microscopy and X-ray powder diffraction in conjunction with density and melting point measurements. For all the compounds investigated, asymmetric ionic metal-carboxylate coordination is proposed, with the molecules located within a triclinic crystal system with P1¯ space group. The molecules are nearly all of similar structure and are arranged within lamellar layers with four molecules per unit cell. The hydrocarbon chains, in nearly all trans conformation, are arranged tail-to-tail and tilted at an average angle of 55 ο to the planes containing lithium ions. The unit cell parameters such as sides: b and c increase linearly with increasing chain length whilst side a shows a linear decrease. Furthermore, the measured densities and melting points show odd-even behaviour, suggesting differences in molecular packing between odd and even chain length homologues. Geometric models are proposed to explain molecular orientation within a lamella and odd-even behaviour, involving the influence of terminal groups on the packing geometry of hydrocarbon chains within the lattice.

Copolymer Synthesis and Characterization by Post-Polymerization Modification

NASA Astrophysics Data System (ADS)

Galvin, Casey James

This PhD thesis examines the physical behavior of surface-grafted polymer assemblies (SGPAs) derived from post-polymerization modification (PPM) reactions in aqueous and vapor enriched environments, and offers an alternative method of creating SGPAs using a PPM approach. SGPAs comprise typically polymer chains grafted covalently to solid substrates. These assemblies show promise in a number of applications and technologies due to the stability imparted by the covalent graft and ability to modify interfacial properties and stability. SGPAs also offer a set of rich physics to explore in fundamental investigations as a result of confining macromolecules to a solid substrate. PPM reactions (also called polymer analogous reactions) apply small molecule organic chemistry reactions to the repeat units of polymer chains in order to generate new chemistries. By applying a PPM strategy to SGPAs, a wide variety of functional groups can be introduced into a small number of well-studied and well-behaved model polymer systems. This approach offers the advantage of holding constant other properties of the SGPA (e.g., molecular weight, MW, and grafting density, sigma) to isolate the effect of chemistry on physical behavior. Using a combination of PPM and fabrication methods that facilitate the formation of SPGAs with position-dependent gradual variation of sigma on flat impenetrable substrate, the influence of polymer chemistry and sigma is examined on the stability of weak polyelectrolyte brushes in aqueous environments at different pH levels. Degrafting of polymer chains in SGPAs exhibits a complex dependence on side chain chemistry, sigma, pH and the charge fraction (alpha) within the brush. Results of these experiments support a proposed mechanism of degrafting, wherein extension of the grafted chains away from the substrate generates tension along the polymer backbone, which activates the grafting chemistry for hydrolysis. The implications of these findings are important in developing technologies that use SGPAs in aqueous environments, and point to a need for potential alternative grafting chemistries. The behavior of SGPAs in vapor environments remains an underexplored phenomenon. By changing systematically the chemistry of SGPAs derived from a parent sample, the influence of side chain functional groups on the swelling of weak and strong polyelectrolyte brushes in the presence of water, methanol and ethanol vapors is explored. The extent of swelling and solvent uptake depends strongly on the chemistry in the polymer side chain and of the solvent. Despite bearing a permanent electrostatic charge in the side chain, the strong polyelectrolyte brushes exhibit no behavior typical of polyelectrolytes in water due to no dissociation of the counterion. Of particular interest is the behavior in humid environments of an SGPA bearing a zwitterionic group in its side chain, which results in exposure of electrostatic charges without counterions. Using substrates bearing the aforementioned sigma gradient of polymeric grafts, evidence of inter- and intramolecular complex formation is presented. Finally, a method of developing SGPAs by polymerizing bulk polymer chains through surface-grafted monomers (SGMs) is described. The SGMs are incorporated onto a solid substrate using the same PPM reaction employed in the degrafting and vapor swelling experiments, highlighting the versatility of PPM. The thickness of these SGPAs is correlated to the bulk polymer chains MW, suggesting this technique can be used in existing industrial bulk polymerization processes.

Correlation between polymer architecture, mesoscale structure and photovoltaic performance in side-chain-modified PAE-PAV:fullerene bulk-heterojunction solar cells

NASA Astrophysics Data System (ADS)

Rathgeber, S.; Kuehnlenz, F.; Hoppe, H.; Egbe, D. A. M.; Tuerk, S.; Perlich, J.; Gehrke, R.

2012-02-01

A poly(arylene-ethynylene)-alt-poly(arylene-vinylene) statistical copolymer carrying linear and branched alkoxy side chains along the conjugated backbone in a random manner, yields, compared to its regular substituted counterparts, an improved performance in polymer:fullerene bulk-heterojunction solar cells. Results obtained from GiWAXS experiments show that the improved performance of the statistical copolymer may be attributed to the following structural characteristics: 1) Well, ordered stacked domains that promote backbone planarization and thus improve the ππ-overlap. 2) Partly face-on alignment of domains relative to the electrodes for an improved active layer electrode charge transfer. Branched side chains seem to promote face-on domain orientation. Most likely they can minimize their unfavorable contact with the interface by just bringing the CH3 groups of the branches into direct contact with the surface so that favorable phenylene-substrate interaction can promote face-on orientation. 3) A more isotropic domain orientation throughout the active layer to ensure that the backbone alignment direction has components perpendicular and parallel to the electrodes in order to compromise between light absorption and efficient intra-chain charge transport.

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

PubMed Central

Wünsch, Matthias; Schröder, David; Fröhr, Tanja; Teichmann, Lisa; Hedwig, Sebastian; Janson, Nils; Belu, Clara; Simon, Jasmin; Heidemeyer, Shari; Holtkamp, Philipp; Rudlof, Jens; Klemme, Lennard; Hinzmann, Alessa; Neumann, Beate; Stammler, Hans-Georg

2017-01-01

The amide moiety of peptides can be replaced for example by a triazole moiety, which is considered to be bioisosteric. Therefore, the carbonyl moiety of an amino acid has to be replaced by an alkyne in order to provide a precursor of such peptidomimetics. As most amino acids have a chiral center at Cα, such amide bond surrogates need a chiral moiety. Here the asymmetric synthesis of a set of 24 N-sulfinyl propargylamines is presented. The condensation of various aldehydes with Ellman’s chiral sulfinamide provides chiral N-sulfinylimines, which were reacted with (trimethylsilyl)ethynyllithium to afford diastereomerically pure N-sulfinyl propargylamines. Diverse functional groups present in the propargylic position resemble the side chain present at the Cα of amino acids. Whereas propargylamines with (cyclo)alkyl substituents can be prepared in a direct manner, residues with polar functional groups require suitable protective groups. The presence of particular functional groups in the side chain in some cases leads to remarkable side reactions of the alkyne moiety. Thus, electron-withdrawing substituents in the Cα-position facilitate a base induced rearrangement to α,β-unsaturated imines, while azide-substituted propargylamines form triazoles under surprisingly mild conditions. A panel of propargylamines bearing fluoro or chloro substituents, polar functional groups, or basic and acidic functional groups is accessible for the use as precursors of peptidomimetics. PMID:29234470

Two-dimensional (2D) infrared correlation study of the structural characterization of a surface immobilized polypeptide film stimulated by pH

NASA Astrophysics Data System (ADS)

Chae, Boknam; Son, Seok Ho; Kwak, Young Jun; Jung, Young Mee; Lee, Seung Woo

2016-11-01

The pH-induced structural changes to surface immobilized poly (L-glutamic acid) (PLGA) films were examined by Fourier transform infrared (FTIR) spectroscopy and two-dimensional (2D) correlation analysis. Significant spectral changes were observed in the FTIR spectra of the surface immobilized PLGA film between pH 6 and 7. The 2D correlation spectra constructed from the pH-dependent FTIR spectra of the surface immobilized PLGA films revealed the spectral changes induced by the alternations of the protonation state of the carboxylic acid group in the PLGA side chain. When the pH was increased from 6 to 8, weak spectral changes in the secondary structure of the PLGA main chain were induced by deprotonation of the carboxylic acid side group.

Arginine: Its pKa value revisited

PubMed Central

Fitch, Carolyn A; Platzer, Gerald; Okon, Mark; Garcia-Moreno E, Bertrand; McIntosh, Lawrence P

2015-01-01

Using complementary approaches of potentiometry and NMR spectroscopy, we have determined that the equilibrium acid dissociation constant (pKa value) of the arginine guanidinium group is 13.8 ± 0.1. This is substantially higher than that of ∼12 often used in structure-based electrostatics calculations and cited in biochemistry textbooks. The revised intrinsic pKa value helps explains why arginine side chains in proteins are always predominantly charged, even at pH values as great as 10. The high pKa value also reinforces the observation that arginine side chains are invariably protonated under physiological conditions of near neutral pH. This occurs even when the guanidinium moiety is buried in a hydrophobic micro-environment, such as that inside a protein or a lipid membrane, thought to be incompatible with the presence of a charged group. PMID:25808204

The Radical SAM enzyme NirJ catalyzes the removal of two propionate side chains during heme d1 biosynthesis.

PubMed

Boss, Linda; Oehme, Ramona; Billig, Susan; Birkemeyer, Claudia; Layer, Gunhild

2017-12-01

Heme d 1 is a modified tetrapyrrole playing an important role in denitrification by acting as the catalytically essential cofactor in the cytochrome cd 1 nitrite reductase of many denitrifying bacteria. In the course of heme d 1 biosynthesis, the two propionate side chains on pyrrole rings A and B of the intermediate 12,18-didecarboxysiroheme are removed from the tetrapyrrole macrocycle. In the final heme d 1 molecule, the propionate groups are replaced by two keto functions. Although it was speculated that the Radical S-adenosyl-l-methionine (SAM) enzyme NirJ might be responsible for the removal of the propionate groups and introduction of the keto functions, this has not been shown experimentally, so far. Here, we demonstrate that NirJ is a Radical SAM enzyme carrying two iron-sulfur clusters. While the N-terminal [4Fe-4S] cluster is essential for the initial SAM cleavage reaction, it is not required for substrate binding. NirJ tightly binds its substrate 12,18-didecarboxysiroheme and, thus, can be purified in complex with the substrate. By using the purified NirJ/substrate complex in an in vitro enzyme activity assay, we show that NirJ indeed catalyzes the removal of the two propionate side chains under simultaneous SAM cleavage. However, under the reaction conditions employed, no keto group formation is observed indicating that an additional cofactor or enzyme is needed for this reaction. © 2017 Federation of European Biochemical Societies.

Isolation and identification of calcium-chelating peptides from Pacific cod skin gelatin and their binding properties with calcium.

PubMed

Wu, Wenfei; Li, Bafang; Hou, Hu; Zhang, Hongwei; Zhao, Xue

2017-12-13

A calcium-chelating peptide is considered to have the ability to improve calcium absorption. In this study, Pacific cod skin gelatin hydrolysates treated with trypsin for 120 min exhibited higher calcium-chelating activity. Sequential chromatography, involving hydroxyapatite affinity chromatography and reversed phase high performance liquid chromatography, was used for the purification of calcium-chelating peptides. Two novel peptides with the typical characteristics of collagen were sequenced as GDKGESGEAGER and GEKGEGGHR based on LC-HRMS/MS, which showed a high affinity to calcium. Calcium-peptide complexation was further characterized by ESI-MS (MS and MS/MS) and FTIR spectroscopy. The results showed that the complexation of the two peptides with calcium was conducted mainly at the ratio of 1 : 1. The amino terminal group and the peptide bond of the peptide backbone as well as the amino group of the lysine side chain and the carboxylate of the glutamate side chain were the possible calcium binding sites for the two peptides. Meanwhile, several amino acid side chain groups, including the hydroxyl (Ser) and carboxylate (Asp) of GDKGESGEAGER and the imine (His) of GEKGEGGHR, were crucial in the complexation. The arginine residue in GEKGEGGHR also participated in the calcium coordination. Additionally, several active fragments with calcium-chelating activity were obtained using MS/MS spectra, including GDKGESGEAGE, GEAGER, GEK, EKG and KGE. This study suggests that gelatin-derived peptides have the potential to be used as a calcium-chelating ingredient to combat calcium deficiency.

Properties, performance and associated hazards of state-of-the-art durable water repellent (DWR) chemistry for textile finishing.

PubMed

Holmquist, H; Schellenberger, S; van der Veen, I; Peters, G M; Leonards, P E G; Cousins, I T

2016-05-01

Following the phase-out of long-chain per- and polyfluoroalkyl substances (PFASs), the textile industry had to find alternatives for side-chain fluorinated polymer based durable water repellent (DWR) chemistries that incorporated long perfluoroalkyl side chains. This phase-out and subsequent substitution with alternatives has resulted in a market where both fluorinated and non-fluorinated DWRs are available. These DWR alternatives can be divided into four broad groups that reflect their basic chemistry: side-chain fluorinated polymers, silicones, hydrocarbons and other chemistries (includes dendrimer and inorganic nanoparticle chemistries). In this critical review, the alternative DWRs are assessed with regards to their structural properties and connected performance, loss and degradation processes resulting in diffuse environmental emissions, and hazard profiles for selected emitted substances. Our review shows that there are large differences in performance between the alternative DWRs, most importantly the lack of oil repellence of non-fluorinated alternatives. It also shows that for all alternatives, impurities and/or degradation products of the DWR chemistries are diffusively emitted to the environment. Our hazard ranking suggests that hydrocarbon based DWR is the most environmentally benign, followed by silicone and side-chain fluorinated polymer-based DWR chemistries. Industrial commitments to reduce the levels of impurities in silicone based and side-chain fluorinated polymer based DWR formulations will lower the actual risks. There is a lack of information on the hazards associated with DWRs, in particular for the dendrimer and inorganic nanoparticle chemistries, and these data gaps must be filled. Until environmentally safe alternatives, which provide the required performance, are available our recommendation is to choose DWR chemistry on a case-by-case basis, always weighing the benefits connected to increased performance against the risks to the environment and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Langmuir-Blodgett Films of Aromatic Schiff’s Bases Functionalized in the Side Chains of Polymethacrylate

DTIC Science & Technology

1991-05-03

Report No. 21 - Latigmuir-Blodgett Films of Aromatic Schiffs Bases , K Fuctionalized in the Side Chains of Polymethacrylate by T. Takahashi, P. Miller...aromatic Schiff’s bases functionalized in the side chains of Polymethacrylate T. Takahashi**, P. Miller*, Y. M. Chen*, L. Samuelson***, D. Galotti, B...has been investigated for polymers in which nonlinear optical (NLO) moieties are attachcd i, the side chain of polymethacrylate (PMA) backbone. Polymer

Direct Determination of Site-Specific Noncovalent Interaction Strengths of Proteins from NMR-Derived Fast Side Chain Motional Parameters.

PubMed

Rajeshwar T, Rajitha; Krishnan, Marimuthu

2017-05-25

A novel approach to accurately determine residue-specific noncovalent interaction strengths (ξ) of proteins from NMR-measured fast side chain motional parameters (O axis 2 ) is presented. By probing the environmental sensitivity of side chain conformational energy surfaces of individual residues of a diverse set of proteins, the microscopic connections between ξ, O axis 2 , conformational entropy (S conf ), conformational barriers, and rotamer stabilities established here are found to be universal among proteins. The results reveal that side chain flexibility and conformational entropy of each residue decrease with increasing ξ and that for each residue type there exists a critical range of ξ, determined primarily by the mean side chain conformational barriers, within which flexibility of any residue can be reversibly tuned from highly flexible (with O axis 2 ∼ 0) to highly restricted (with O axis 2 ∼ 1) by increasing ξ by ∼3 kcal/mol. Beyond this critical range of ξ, both side chain flexibility and conformational entropy are insensitive to ξ. The interrelationships between conformational dynamics, conformational entropy, and noncovalent interactions of protein side chains established here open up new avenues to probe perturbation-induced (for example, ligand-binding, temperature, pressure) changes in fast side chain dynamics and thermodynamics of proteins by comparing their conformational energy surfaces in the native and perturbed states.

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations

PubMed Central

Ahlstrom, Logan S.; Vorontsov, Ivan I.; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations. PMID:28107510

Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations.

PubMed

Ahlstrom, Logan S; Vorontsov, Ivan I; Shi, Jun; Miyashita, Osamu

2017-01-01

Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.

SPPS of protected peptidyl aminoalkyl amides.

PubMed

Karavoltsos, Manolis; Mourtas, Spyros; Gatos, Dimitrios; Barlos, Kleomenis

2002-11-01

Monophthaloyl diamines derived from naturally occurring amino acids were attached through their free amino functions to resins of the trityl type. The phthaloyl groups were removed by hydrazinolysis, and peptide chains were assembled using Fmoc/tBu-amino acids on the liberated amino functions. The peptidyl aminoalkyl amides obtained were cleaved from the resins by mild acidolysis, with the tBu-side chain protection remaining intact.

Molecular Design for Preparation of Hexagonal-Ordered Porous Films Based on Side-chain Type Liquid-Crystalline Star Polymer.

PubMed

Naka, Yumiko; Takayama, Hiromu; Koyama, Teruhisa; Le, Khoa V; Sasaki, Takeo

2018-05-02

Fabrication of regularly porous films by the breath-figure method has attracted much attention. The simple, low-cost technique uses the condensation of water droplets to produce these structures, but the phenomenon itself is complex, requiring control over many interacting parameters that change throughout the process. Developing a unified understanding for the molecular design of polymers to prepare ordered porous films is challenging, but required for further advancements. In this article, the effects of the chemical structure of polymers in the breath-figure technique were systematically explored using side-chain type liquid-crystalline (LC) star polymers. The formation of porous films was affected by the structure of the polymers. Although the entire film surface of poly(11-[4-(4-cyanobiphenyl)oxy]undecyl methacrylate) (P11CB) had a hexagonal ordered porous structure over a certain Mn value, regularly arranged holes did not easily form in poly(methyl methacrylate) (PMMA), even though the main chain of PMMA is similar to that of P11CB. Comparing P11CB and poly(11-[(1,1'-biphenyl)-4-yloxy]undecyl methacrylate) (P11B) (P11CB without cyano groups) showed that the local polar groups in hydrophobic polymers promoted the formation of ordered porous films. No holes formed in poly(4-cyanobiphenyl methacrylate) (P0CB) (P11CB without alkyl spacers) films due to its hydrophilicity. The introduction of alkyl chains in P0CB allowed the preparation of honeycomb-structured films by increasing the internal tension. However, alkyl chains in the side chain alone did not result in a porous structure, as in the case of poly(11-[(1,1'-biphenyl)-4-yloxy]undecyl methacrylate) (P11). Aromatic rings are also required to increase the Tg and improve film formability. In the present study, suitable molecular designs of polymers were found, specifically hydrophobic polymers with local polar groups, to form a regularly porous structure. Development of clear guidelines for the molecular design of polymers is the subject of our current research, which will enable the fabrication of porous films using various functional polymers.

The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells

PubMed Central

Francis, Brian R.

2015-01-01

Although analysis of the genetic code has allowed explanations for its evolution to be proposed, little evidence exists in biochemistry and molecular biology to offer an explanation for the origin of the genetic code. In particular, two features of biology make the origin of the genetic code difficult to understand. First, nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles. This paper advances the hypothesis that the earliest predecessor of the nucleic acids was a β-linked polyester made from malic acid, a highly conserved metabolite in the carboxylic acid cycles. In the β-linked polyester, the side chains are carboxylic acid groups capable of forming interstrand double hydrogen bonds. Evolution of the nucleic acids involved changes to the backbone and side chain of poly(β-d-malic acid). Conversion of the side chain carboxylic acid into a carboxamide or a longer side chain bearing a carboxamide group, allowed information polymers to form amide pairs between polyester chains. Aminoacylation of the hydroxyl groups of malic acid and its derivatives with simple amino acids such as glycine and alanine allowed coupling of polyester synthesis and protein synthesis. Use of polypeptides containing glycine and l-alanine for activation of two different monomers with either glycine or l-alanine allowed simple coded autocatalytic synthesis of polyesters and polypeptides and established the first genetic code. A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed. The cell consists of an iron-sulfide particle enclosed by tholin, a heterogeneous organic material that is produced by Miller-Urey type experiments that simulate conditions on the early Earth. As the synthesis of nucleic acids evolved from β-linked polyesters, the singlet coding system for replication evolved into a four nucleotide/four amino acid process (AMP = aspartic acid, GMP = glycine, UMP = valine, CMP = alanine) and then into the triplet ribosomal process that permitted multiple copies of protein to be synthesized independent of replication. This hypothesis reconciles the “genetics first” and “metabolism first” approaches to the origin of life and explains why there are four bases in the genetic alphabet. PMID:25679748

A Markov Random Field Framework for Protein Side-Chain Resonance Assignment

NASA Astrophysics Data System (ADS)

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

Nuclear magnetic resonance (NMR) spectroscopy plays a critical role in structural genomics, and serves as a primary tool for determining protein structures, dynamics and interactions in physiologically-relevant solution conditions. The current speed of protein structure determination via NMR is limited by the lengthy time required in resonance assignment, which maps spectral peaks to specific atoms and residues in the primary sequence. Although numerous algorithms have been developed to address the backbone resonance assignment problem [68,2,10,37,14,64,1,31,60], little work has been done to automate side-chain resonance assignment [43, 48, 5]. Most previous attempts in assigning side-chain resonances depend on a set of NMR experiments that record through-bond interactions with side-chain protons for each residue. Unfortunately, these NMR experiments have low sensitivity and limited performance on large proteins, which makes it difficult to obtain enough side-chain resonance assignments. On the other hand, it is essential to obtain almost all of the side-chain resonance assignments as a prerequisite for high-resolution structure determination. To overcome this deficiency, we present a novel side-chain resonance assignment algorithm based on alternative NMR experiments measuring through-space interactions between protons in the protein, which also provide crucial distance restraints and are normally required in high-resolution structure determination. We cast the side-chain resonance assignment problem into a Markov Random Field (MRF) framework, and extend and apply combinatorial protein design algorithms to compute the optimal solution that best interprets the NMR data. Our MRF framework captures the contact map information of the protein derived from NMR spectra, and exploits the structural information available from the backbone conformations determined by orientational restraints and a set of discretized side-chain conformations (i.e., rotamers). A Hausdorff-based computation is employed in the scoring function to evaluate the probability of side-chain resonance assignments to generate the observed NMR spectra. The complexity of the assignment problem is first reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is used to find a set of optimal side-chain resonance assignments that best fit the NMR data. We have tested our algorithm on NMR data for five proteins, including the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), human ubiquitin, the ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta (pol η UBZ), and the human Set2-Rpb1 interacting domain (hSRI). Our algorithm assigns resonances for more than 90% of the protons in the proteins, and achieves about 80% correct side-chain resonance assignments. The final structures computed using distance restraints resulting from the set of assigned side-chain resonances have backbone RMSD 0.5 - 1.4 Å and all-heavy-atom RMSD 1.0 - 2.2 Å from the reference structures that were determined by X-ray crystallography or traditional NMR approaches. These results demonstrate that our algorithm can be successfully applied to automate side-chain resonance assignment and high-quality protein structure determination. Since our algorithm does not require any specific NMR experiments for measuring the through-bond interactions with side-chain protons, it can save a significant amount of both experimental cost and spectrometer time, and hence accelerate the NMR structure determination process.

Influence of side chain conformation and configuration on glycosyl donor reactivity and selectivity as illustrated by sialic acid donors epimeric at the 7-position.

PubMed

Kancharla, Pavan K; Crich, David

2013-12-18

Two N-acetyl 4O,5N-oxazolidinone-protected sialyl thioglycosides epimeric at the 7-position have been synthesized and their reactivity and stereoselectivity in glycosylation reactions have been compared. It is demonstrated that the natural 7S-donor is both more reactive and more α-selective than the unnatural 7R-isomer. The difference in reactivity is attributed to the side chain conformation and specifically to the proximity of O7 to the anomeric center. In the natural 7S-isomer, O7 is closer to the anomeric center than in its unnatural 7R-epimer and, therefore, better able to support incipient positive charge at the locus of reaction. The difference in selectivity is also attributed to the side conformation, which in the unnatural 7R-series is placed perpendicularly above the α-face of the donor and so shields it to a greater extent than in the 7S-series. These observations are consistent with earlier conclusions on the influence of the side chain conformation on reactivity and selectivity derived from conformationally locked models in the glucose and galactose series and corroborate the suggestion that those effects are predominantly stereoelectronic rather than torsional. The possible relevance of side chain conformation as a factor in the influence of glycosylation stereoselectivity by remote protecting groups and as a control element in enzymic processes for glycosidic bond formation and hydrolysis are discussed. Methods for assignment of the anomeric configuration in the sialic acid glycosides are critically surveyed.

The three-dimensional structure of a complex of a murine Fab (NC10. 14) with a potent sweetener (NC174): an illustration of structural diversity in antigen recognition by immunoglobulins.

PubMed

Guddat, L W; Shan, L; Broomell, C; Ramsland, P A; Fan, Z; Anchin, J M; Linthicum, D S; Edmundson, A B

2000-09-29

The three-dimensional structure of a complex of an Fab from a murine IgG2b(lambda) antibody (NC10.14) with a high potency sweet tasting hap- ten, N-(p-cyanophenyl)-N'-(diphenylmethyl)-N"-(carboxymethyl)guan idine (NC174), has been determined to 2.6 A resolution by X-ray crystallography. This complex crystallized in the triclinic space group P1, with two molecules in the asymmetric unit. In contrast to a companion monoclonal antibody (NC6.8) with a kappa-type light chain and similar high affinity for the NC174 ligand, the NC10.14 antibody possessed a large and deep antigen combining site bounded primarily by the third complementarity-determining regions (CDR3s) of the light and heavy chains. CDR3 of the heavy chain dominated the site and its crown protruded into the external solvent as a type 1' beta-turn. NC174 was nested against HCDR3 and was held in place by two tryptophan side-chains (L91 and L96) from LCDR3. The diphenyl rings were accommodated on an upper tier of the binding pocket that is largely hydrophobic. At the floor of the site, a positively charged arginine side-chain (H95) stabilized the orientation of the electronegative cyano group of the hapten. The negative charge on the acetate group was partially neutralized by a hydrogen bond with the phenolic hydroxyl group of tyrosine H58. Comparisons of the modes of binding of NC174 to the NC6.8 and NC10.14 antibodies illustrate the enormous structural and mechanistic diversity manifest by immune responses. Copyright 2000 Academic Press.

Porphyrins and metal complexes thereof having haloalkyl side chains

DOEpatents

Wijesekera, Tilak; Lyons, James E.; Ellis, Jr., Paul E.; Bhinde, Manoj V.

1997-01-01

Transition metal complexes of meso-haloalkylporphyrins, wherein the haloalkyl groups contain 2 to 8 carbon atoms have been found to be highly effective catalysts for oxidation of alkanes and for the decomposition of hydroperoxides.

UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part 2: selected applications.

PubMed

Antosiewicz, Jan M; Shugar, David

In Part 2 we discuss application of several different types of UV-Vis spectroscopy, such as normal, difference, and second-derivative UV absorption spectroscopy, fluorescence spectroscopy, linear and circular dichroism spectroscopy, and Raman spectroscopy, of the side-chain of tyrosine residues in different molecular environments. We review the ways these spectroscopies can be used to probe complex protein structures.

UV-Vis spectroscopy of tyrosine side-groups in studies of protein structure. Part 2: selected applications.

PubMed

Antosiewicz, Jan M; Shugar, David

2016-06-01

In Part 2 we discuss application of several different types of UV-Vis spectroscopy, such as normal, difference, and second-derivative UV absorption spectroscopy, fluorescence spectroscopy, linear and circular dichroism spectroscopy, and Raman spectroscopy, of the side-chain of tyrosine residues in different molecular environments. We review the ways these spectroscopies can be used to probe complex protein structures.

Antibody side chain conformations are position-dependent.

PubMed

Leem, Jinwoo; Georges, Guy; Shi, Jiye; Deane, Charlotte M

2018-04-01

Side chain prediction is an integral component of computational antibody design and structure prediction. Current antibody modelling tools use backbone-dependent rotamer libraries with conformations taken from general proteins. Here we present our antibody-specific rotamer library, where rotamers are binned according to their immunogenetics (IMGT) position, rather than their local backbone geometry. We find that for some amino acid types at certain positions, only a restricted number of side chain conformations are ever observed. Using this information, we are able to reduce the breadth of the rotamer sampling space. Based on our rotamer library, we built a side chain predictor, position-dependent antibody rotamer swapper (PEARS). On a blind test set of 95 antibody model structures, PEARS had the highest average χ 1 and χ1+2 accuracy (78.7% and 64.8%) compared to three leading backbone-dependent side chain predictors. Our use of IMGT position, rather than backbone ϕ/ψ, meant that PEARS was more robust to errors in the backbone of the model structure. PEARS also achieved the lowest number of side chain-side chain clashes. PEARS is freely available as a web application at http://opig.stats.ox.ac.uk/webapps/pears. © 2018 Wiley Periodicals, Inc.

Effect of plasma membrane fluidity on serotonin transport by endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Block, E.R.; Edwards, D.

1987-11-01

To evaluate the effect of plasma membrane fluidity of lung endothelial cells on serotonin transport, porcine pulmonary artery endothelial cells were incubated for 3 h with either 0.1 mM cholesterol hemisuccinate, 0.1 mM cis-vaccenic acid, or vehicle (control), after which plasma membrane fluidity and serotinin transport were measured. Fluorescence spectroscopy was used to measure fluidity in the plasma membrane. Serotonin uptake was calculated from the disappearance of ({sup 14}C)-serotonin from the culture medium. Cholesterol decreased fluidity in the subpolar head group and central and midacyl side-chain regions of the plasma membrane and decreased serotonin transport, whereas cis-vaccenic acid increased fluiditymore » in the central and midacyl side-chain regions of the plasma membrane and also increased serotonin transport. Cis-vaccenic acid had no effect of fluidity in the subpolar head group region of the plasma membrane. These results provide evidence that the physical state of the central and midacyl chains within the pulmonary artery endothelial cell plasma membrane lipid bilayer modulates transmembrane transport of serotonin by these cells.« less

Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines.

PubMed

Bjedov, Srđan; Jakimov, Dimitar; Pilipović, Ana; Poša, Mihalj; Sakač, Marija

2017-04-01

Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC 50 <5µM. Altering carboxylic group to amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Molecular Flexibility upon Ice Adhesion Shear Strength

NASA Technical Reports Server (NTRS)

Smith, Joseph G.; Wohl, Christopher J.; Kreeger, Richard E.; Palacios, Jose; Knuth, Taylor; Hadley, Kevin

2016-01-01

Ice formation on aircraft surfaces effects aircraft performance by increasing weight and drag leading to loss of lift. Current active alleviation strategies involve pneumatic boots, heated surfaces, and usage of glycol based de-icing fluids. Mitigation or reduction of in-flight icing by means of a passive approach may enable retention of aircraft capabilities, i.e., no reduction in lift, while reducing the aircraft weight and mechanical complexity. Under a NASA Aeronautics Research Institute Seedling activity, the effect of end group functionality and chain length upon ice adhesion shear strength (IASS) was evaluated with the results indicating that chemical functionality and chain length (i.e. molecular flexibility) affected IASS. Based on experimental and modeling results, diamine monomers incorporating molecular flexibility as either a side chain or in between diamine functionalities were prepared, incorporated into epoxy resins that were subsequently used to fabricate coatings on aluminum substrates, and tested in a simulated icing environment. The IASS was found to be lower when molecular flexibility was incorporated in the polymer chain as opposed to a side chain.

Influence of Protein Scaffold on Side-Chain Transfer Free Energies.

PubMed

Marx, Dagen C; Fleming, Karen G

2017-08-08

The process by which membrane proteins fold involves the burial of side chains into lipid bilayers. Both structure and function of membrane proteins depend on the magnitudes of side-chain transfer free energies (ΔΔG sc o ). In the absence of other interactions, ΔΔG sc o is an independent property describing the energetics of an isolated side chain in the bilayer. However, in reality, side chains are attached to the peptide backbone and surrounded by other side chains in the protein scaffold in biology, which may alter the apparent ΔΔG sc o . Previously we reported a whole protein water-to-bilayer hydrophobicity scale using the transmembrane β-barrel Escherichia coli OmpLA as a scaffold protein. To investigate how a different protein scaffold can modulate these energies, we measured ΔΔG sc o for all 20 amino acids using the transmembrane β-barrel E. coli PagP as a scaffold protein. This study represents, to our knowledge, the first instance of ΔΔG sc o measured in the same experimental conditions in two structurally and sequentially distinct protein scaffolds. Although the two hydrophobicity scales are strongly linearly correlated, we find that there are apparent scaffold induced changes in ΔΔG sc o for more than half of the side chains, most of which are polar residues. We propose that the protein scaffold affects the ΔΔG sc o of side chains that are buried in unfavorable environments by dictating the mechanisms by which the side chain can reach a more favorable environment and thus modulating the magnitude of ΔΔG sc o . Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A Solid-State Deuterium NMR and SFG Study of the Side Chain Dynamics of Peptides Adsorbed onto Surfaces

PubMed Central

Breen, Nicholas F.; Weidner, Tobias; Li, Kun; Castner, David G.; Drobny, Gary P.

2011-01-01

The artificial amphiphilic peptide LKα14 adopts a helical structure at interfaces, with opposite orientation of its leucine (L, hydrophobic) and lysine (K, hydrophilic) side chains. When adsorbed onto surfaces, different residue side chains necessarily have different proximities to the surface, depending on both their position in the helix and the composition of the surface itself. Deuterating the individual leucine residues (isopropyl-d7) permits the use of solid-state deuterium NMR as a site-specific probe of side chain dynamics. In conjunction with SFG as a probe of the peptide binding face, we demonstrate that the mobility of specific leucine side chains at the interface is quantifiable in terms of their surface proximity. PMID:19764755

Assessment of Protein Side-Chain Conformation Prediction Methods in Different Residue Environments

PubMed Central

Peterson, Lenna X.; Kang, Xuejiao; Kihara, Daisuke

2016-01-01

Computational prediction of side-chain conformation is an important component of protein structure prediction. Accurate side-chain prediction is crucial for practical applications of protein structure models that need atomic detailed resolution such as protein and ligand design. We evaluated the accuracy of eight side-chain prediction methods in reproducing the side-chain conformations of experimentally solved structures deposited to the Protein Data Bank. Prediction accuracy was evaluated for a total of four different structural environments (buried, surface, interface, and membrane-spanning) in three different protein types (monomeric, multimeric, and membrane). Overall, the highest accuracy was observed for buried residues in monomeric and multimeric proteins. Notably, side-chains at protein interfaces and membrane-spanning regions were better predicted than surface residues even though the methods did not all use multimeric and membrane proteins for training. Thus, we conclude that the current methods are as practically useful for modeling protein docking interfaces and membrane-spanning regions as for modeling monomers. PMID:24619909

Phase separation of comb polymer nanocomposite melts.

PubMed

Xu, Qinzhi; Feng, Yancong; Chen, Lan

2016-02-07

In this work, the spinodal phase demixing of branched comb polymer nanocomposite (PNC) melts is systematically investigated using the polymer reference interaction site model (PRISM) theory. To verify the reliability of the present method in characterizing the phase behavior of comb PNCs, the intermolecular correlation functions of the system for nonzero particle volume fractions are compared with our molecular dynamics simulation data. After verifying the model and discussing the structure of the comb PNCs in the dilute nanoparticle limit, the interference among the side chain number, side chain length, nanoparticle-monomer size ratio and attractive interactions between the comb polymer and nanoparticles in spinodal demixing curves is analyzed and discussed in detail. The results predict two kinds of distinct phase separation behaviors. One is called classic fluid phase boundary, which is mediated by the entropic depletion attraction and contact aggregation of nanoparticles at relatively low nanoparticle-monomer attraction strength. The second demixing transition occurs at relatively high attraction strength and involves the formation of an equilibrium physical network phase with local bridging of nanoparticles. The phase boundaries are found to be sensitive to the side chain number, side chain length, nanoparticle-monomer size ratio and attractive interactions. As the side chain length is fixed, the side chain number has a large effect on the phase behavior of comb PNCs; with increasing side chain number, the miscibility window first widens and then shrinks. When the side chain number is lower than a threshold value, the phase boundaries undergo a process from enlarging the miscibility window to narrowing as side chain length increases. Once the side chain number overtakes this threshold value, the phase boundary shifts towards less miscibility. With increasing nanoparticle-monomer size ratio, a crossover of particle size occurs, above which the phase separation is consistent with that of chain PNCs. The miscibility window for this condition gradually narrows while the other parameters of the PNCs system are held constant. These results indicate that the present PRISM theory can give molecular-level details of the underlying mechanisms of the comb PNCs. It is hoped that the results can be used to provide useful guidance for the future design control of novel, thermodynamically stable comb PNCs.

Motion of spin label side chains in cellular retinol-binding protein: correlation with structure and nearest-neighbor interactions in an antiparallel beta-sheet.

PubMed

Lietzow, Michael A; Hubbell, Wayne L

2004-03-23

A goal in the development of site-directed spin labeling in proteins is to correlate the motion of a nitroxide side chain with local structure, interactions, and dynamics. Significant progress toward this goal has been made using alpha-helical proteins of known structure, and the present study is the first step in a similar exploration of a beta-sheet protein, cellular retinol-binding protein (CRBP). Nitroxide side chains were introduced along both interior and edge strands. At sites in interior strands, the side-chain motion is strongly influenced by interactions with side chains of neighboring strands, giving rise to a rich variety of dynamic modes (weakly ordered, strongly ordered, immobilized) and complex electron paramagnetic resonance spectra that are modulated by strand twist. The interactions giving rise to the dynamic modes are explored using mutagenesis, and the results demonstrate the particular importance of the non-hydrogen-bonded neighbor residue in giving rise to highly ordered states. Along edge strands of the beta-sheet, the motion of the side chain is simple and weakly ordered, resembling that at solvent-exposed surfaces of an alpha-helix. A simple working model is proposed that can account for the wide variety of dynamic modes encountered. Collectively, the results suggest that the nitroxide side chain is an effective probe of side-chain interactions, and that site-directed spin labeling should be a powerful means of monitoring conformational changes that involve changes in beta-sheet topology.

Tuning Thermoresponsive Properties of Cationic Elastin-like Polypeptides by Varying Counterions and Side-Chains.

PubMed

Petitdemange, Rosine; Garanger, Elisabeth; Bataille, Laure; Bathany, Katell; Garbay, Bertrand; Deming, Timothy J; Lecommandoux, Sébastien

2017-05-17

We report the synthesis of methionine-containing recombinant elastin-like polypeptides (ELPs) of different lengths that contain periodically spaced methionine residues. These ELPs were chemoselectively alkylated at all methionine residues to give polycationic derivatives. Some of these samples were found to possess solubility transitions in water, where the temperature of these transitions varied with ELP concentration, nature of the methionine alkylating group, and nature of the sulfonium counterions. These studies show that introduction and controlled spacing of methionine sulfonium residues into ELPs can be used as a means both to tune their solubility transition temperatures in water using a variety of different parameters and to introduce new side-chain functionality.

Penicillin and Beta-Lactam Hypersensitivity.

PubMed

Har, Daniel; Solensky, Roland

2017-11-01

Ten percent of patients report penicillin allergy, but more than 90% of these individuals can tolerate penicillins. Skin testing remains the optimal method for evaluation of possible IgE-mediated penicillin allergy and is recommended by professional societies, as the harms for alternative antibiotics include antimicrobial resistance, prolonged hospitalizations, readmissions, and increased costs. Removal of penicillin allergy leads to decreased utilization of broad-spectrum antibiotics, such as fluoroquinolones and vancomycin. There is minimal allergic cross-reactivity between penicillins and cephalosporins. IgE-mediated allergy to cephalosporins is usually side-chain specific and may warrant graded challenge with cephalosporins containing dissimilar R1 or R2 group side chains. Copyright © 2017 Elsevier Inc. All rights reserved.

Porphyrins and metal complexes thereof having haloalkyl side chains

DOEpatents

Wijesekera, T.; Lyons, J.E.; Ellis, P.E. Jr.; Bhinde, M.V.

1997-03-04

Transition metal complexes of meso-haloalkylporphyrins, wherein the haloalkyl groups contain 2 to 8 carbon atoms have been found to be highly effective catalysts for oxidation of alkanes and for the decomposition of hydroperoxides. 7 figs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rock, C.D.; Zeevaart, J.A.D.

We have isolated ABA-aldehyde and ABA-t-diol from postharvest apple fruits, cv. Granny Smith and confirmed their structure by GC-MS. These putative ABA biosynthetic precursors incorporate {sup 18}O to a similar degree as ABA during 48 hours under {sup 18}O{sub 2} atmospheres. The presence of significant amounts of ABA-aldehyde can explain the unique {sup 18}O labeling pattern of ABA in this tissue, where a majority of ABA molecules containing {sup 18}O is labeled in the 1{prime}-hydroxyl group and not in the side chain carboxyl group, the primary site of incorporation for stressed leaves. Exchange of the carbonyl oxygen of ABA-aldehyde withmore » water would decrease {sup 18}O enrichment in the side chain. Results of {sup 18}O{sub 2} experiments and feeding studies using hexadeutero-ABA-aldehyde will be presented and the biosynthetic relationship of these compounds discussed.« less

Discovery of 2-azetidinone and 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain as potential cholesterol absorption inhibitors.

PubMed

Yuan, Xinrui; Lu, Peng; Xue, Xiaojian; Qin, Hui; Fan, Chen; Wang, Yubin; Zhang, Qi

2016-02-01

Cholesterol absorption inhibitor (CAI) targeting Niemann-Pick C1-like1 protein was developed for the treatment of hyperlipidaemia and only ezetimibe was approved so far. For developing novel CAIs, we synthesized sixteen 2-azetidinone derivatives and thirteen 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain, and their inhibitory activity of cholesterol absorption was evaluated in Caco-2 cell line in vitro. Furthermore, top six compounds were measured by cytotoxicity and partition coefficient, and 2-azetidinone analogue 9e was selected for in vivo study. Finally, 9e considerably reduced total cholesterol, LDL-C, FFA and triglyceride in the serum and increased the rate of HDL-C to total cholesterol, suggesting it could regulate the lipid metabolism and act as a potent CAI. Copyright © 2015 Elsevier Ltd. All rights reserved.

Synthesis, reactivity and application studies for different biolubricants

PubMed Central

2014-01-01

Vegetable oils have different unique properties owing to their unique chemical structure. Vegetable oils have a greater ability to lubricate and have higher viscosity indices. Therefore, they are being more closely examined as base oil for biolubricants and functional fluids. In spite of their many advantages, vegetable oils suffer from two major drawbacks of inadequate oxidative stability and poor low-temperature properties, which hinder their utilization as biolubricant base oils. Transforming alkene groups in fatty acids to other stable functional groups could improve the oxidative stability, whereas reducing structural uniformity of the oil by attaching alkyl side chains could improve the low-temperature performance. In that light, the epoxidation of unsaturated fatty acids is very interesting as it can provide diverse side chains arising from the mono- or di-epoxidation of the unsaturated fatty acid. Oxirane ring opening by an acid-catalyzed reaction with a suitable reagent provides interesting polyfunctional compounds. PMID:24612780

Resonant electron capture by aspartame and aspartic acid molecules.

PubMed

Muftakhov, M V; Shchukin, P V

2016-12-30

The processes for dissociative electron capture are the key mechanisms for decomposition of biomolecules, proteins in particular, under interaction with low-energy electrons. Molecules of aspartic acid and aspartame, i.e. modified dipeptides, were studied herein to define the impact of the side functional groups on peptide chain decomposition in resonant electron-molecular reactions. The processes of formation and decomposition of negative ions of both aspartame and aspartic acid were studied by mass spectrometry of negative ions under resonant electron capture. The obtained mass spectra were interpreted under thermochemical analysis by quantum chemical calculations. Main channels of negative molecular ions fragmentation were found and characteristic fragment ions were identified. The СООН fragment of the side chain in aspartic acid is shown to play a key role like the carboxyl group in amino acids and aliphatic oligopeptides. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

PubMed

Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

1998-01-15

We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

Flomoxef, a new oxacephem antibiotic, does not cause hemostatic defects.

PubMed

Cazzola, M; Brancaccio, V; De Giglio, C; Paternò, E; Matera, M G; Rossi, F

1993-03-01

Antibiotics of the beta-lactam class may cause coagulation defects and bleeding. It has been suggested that N-methyltetrazolethiol (NMTT), a common side chain group at the 3'-position of the cephem or 1-oxacephem frame, could be responsible for the hypoprothrombinemic effect of the antibiotics and that it could inhibit the liver vitamin K-epoxide reductase activity. Flomoxef (6315-S) is a new oxacephem antibiotic which differs from latamoxef because it has [1-(2-hydroxethyl)-1H-tetrazol-5-yl] thiomethyl (HTT) as a side chain at the 3'-position of cephem group instead of NMTT and an extensive modification of 7 beta-acylamino side chain. The present study was carried out to study its effects on vitamin K-dependent blood coagulation parameters in human volunteers. Ten adult patients (6 men and 4 women), suffering from chronic bronchitis, entered into the study. Each patient received ten 1 g i.m. injections of flomoxef at 12-hourly intervals. Apparently, the treatment with this oxacephem antibiotic had no significant effect. PT, PTT and fibrinogen remained in the normal range in all patients and factors II+VII+X, protein C, protein S and AT III were not depleted. The trend was similar both in men and women. Based on the results of the present study, we conclude that flomoxef is an antibiotic that does not exhibit an effect on blood coagulation, even in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Precise structural analysis of α-helical polypeptide by quantum-chemical calculation related to reciprocal side-chain combination of two L-phenylalanine residues

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Kurosu, Hiromichi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a series of well-defined α-helical octadecapeptides composed of two L-phenylalanine (Phe) and 16 L-alanine (Ala) residues, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy calculation and the precise secondary structural analysis, we found that the conformational stability of the α-helix is closely related to the reciprocal side-chain combinations (such as positional relation and side-chain conformation) of two Phe residues in this system. Furthermore, we demonstrated that the 1H, 13C, 15N and 17O isotropic chemical shifts of each Phe residue depend on the respective side-chain conformations of the Phe residue.

Side-chain-side-chain interactions and stability of the helical state

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.

Solution structure of a small protein containing a fluorinated side chain in the core

PubMed Central

Cornilescu, Gabriel; Hadley, Erik B.; Woll, Matthew G.; Markley, John L.; Gellman, Samuel H.; Cornilescu, Claudia C.

2007-01-01

We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe → F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe → F5-Phe mutations are interesting because aryl–perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl–aryl or perfluoroaryl–perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 → F5-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by ∼1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe → F5-Phe mutations offer the possibility of greater tertiary structural stability from side chain–side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability. PMID:17123960

Amide I vibrational mode suppression in surface (SERS) and tip (TERS) enhanced Raman spectra of protein specimens

PubMed Central

Kurouski, Dmitry; Postiglione, Thomas; Deckert-Gaudig, Tanja; Deckert, Volker; Lednev, Igor K.

2013-01-01

Surface- and tip-enhanced Raman spectroscopy (SERS and TERS) are modern spectroscopic techniques, which are becoming widely used and show a great potential for the structural characterisation of biological systems. Strong enhancement of the Raman signal through localised surface plasmon resonance enables chemical detection at the single-molecule scale. Enhanced Raman spectra collected from biological specimens, such as peptides, proteins or microorganisms, were often observed to lack the amide I band, which is commonly used as a marker for the interpretation of secondary protein structure. The cause of this phenomenon was unclear for many decades. In this work, we investigated this phenomenon for native insulin and insulin fibrils using both TERS and SERS and compared these spectra to the spectra of well-defined homo peptides. The results indicate that the appearance of the amide I Raman band does not correlate with the protein aggregation state, but is instead determined by the size of the amino acid side chain. For short model peptides, the absence of the amide I band in TERS and SERS spectra correlates with the presence of a bulky side chain. Homo-glycine and -alanine, which are peptides with small side chain groups (H and CH3, respectively), exhibited an intense amide I band in almost 100% of the acquired spectra. Peptides with bulky side chains, such as tyrosine and tryptophan, exhibited the amide I band in 70% and 31% of the acquired spectra, respectively. PMID:23330149

Applying Thienyl Side Chains and Different π-Bridge to Aromatic Side-Chain Substituted Indacenodithiophene-Based Small Molecule Donors for High-Performance Organic Solar Cells.

PubMed

Wang, Jin-Liang; Liu, Kai-Kai; Liu, Sha; Liu, Feng; Wu, Hong-Bin; Cao, Yong; Russell, Thomas P

2017-06-14

A pair of linear tetrafluorinated small molecular donors, named as ThIDTTh4F and ThIDTSe4F, which are with tetrathienyl-substituted IDT as electron-rich central core, electron-deficient difluorobenzothiadiazole as acceptor units, and donor end-capping groups, but having differences in the π-bridge (thiophene and selenophene), were successfully synthesized and evaluated as donor materials in organic solar cells. Such π-bridge and core units in these small molecules play a decisive role in the formation of the nanoscale separation of the blend films, which were systematically investigated through absorption spectra, grazing incidence X-ray diffraction pattern, transmission electron microscopy images, resonant soft X-ray scattering profiles, and charge mobility measurement. The ThIDTSe4F (with selenophene π-bridge)-based device exhibited superior performance than devices based on ThIDTh4F (with thiophene π-bridge) after post annealing treatment owing to optimized film morphology and improved charge transport. Power conversion efficiency of 7.31% and fill factor of ∼0.70 were obtained by using a blend of ThIDTSe4F and PC 71 BM with thermal annealing and solvent vapor annealing treatments, which is the highest PCE from aromatic side-chain substituted IDT-based small molecular solar cells. The scope of this study is to reveal the structure-property relationship of the aromatic side-chain substituted IDT-based donor materials as a function of π-bridge and the post annealing conditions.

Synthesis and analgesic activity of some side-chain modified anpirtoline derivatives.

PubMed

Rádl, S; Hezky, P; Proska, J; Hejnová, L; Krejcí, I

2000-05-01

New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.

Searching for low percolation thresholds within amphiphilic polymer membranes: The effect of side chain branching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorenbos, G., E-mail: dorenbos@ny.thn.ne.jp

Percolation thresholds for solvent diffusion within hydrated model polymeric membranes are derived from dissipative particle dynamics in combination with Monte Carlo (MC) tracer diffusion calculations. The polymer backbones are composed of hydrophobic A beads to which at regular intervals Y-shaped side chains are attached. Each side chain is composed of eight A beads and contains two identical branches that are each terminated with a pendant hydrophilic C bead. Four types of side chains are considered for which the two branches (each represented as [C], [AC], [AAC], or [AAAC]) are splitting off from the 8th, 6th, 4th, or 2nd A bead,more » respectively. Water diffusion through the phase separated water containing pore networks is deduced from MC tracer diffusion calculations. The percolation threshold for the architectures containing the [C] and [AC] branches is at a water volume fraction of ∼0.07 and 0.08, respectively. These are much lower than those derived earlier for linear architectures of various side chain length and side chain distributions. Control of side chain architecture is thus a very interesting design parameter to decrease the percolation threshold for solvent and proton transports within flexible amphiphilic polymer membranes.« less

Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of a tunable molecular bottlebrush scaffold

DOE PAGES

Ahn, Suk-kyun; Carrillo, Jan-Michael Y.; Keum, Jong K.; ...

2017-04-07

The ability to widely tune the design of macromolecular bottlebrushes provides access to self-assembled nanostructures formed by microphase segregation in melt, thin film and solution that depart from structures adopted by simple linear copolymers. A series of random bottlebrush copolymers containing poly(3-hexylthiophene) (P3HT) and poly(D,L-lactide) (PLA) side chains grafted on a poly(norbornene) backbone were synthesized via ring-opening metathesis polymerization (ROMP) using the grafting through approach. P3HT side chains induce a physical aggregation of the bottlebrush copolymers upon solvent removal by vacuum drying, primarily driven by attractive π–π interactions; however, the amount of aggregation can be controlled by adjusting side chainmore » composition or by adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular dynamics simulations reveal that linear P3HT chains preferentially associate with P3HT side chains of bottlebrush copolymers, which tends to reduce the aggregation. The nanoscale morphology of microphase segregated thin films created by casting P3HT–PLA random bottlebrush copolymers is highly dependent on the composition of P3HT and PLA side chains, while domain spacing of nanostructures is mainly determined by the length of the side chains. The selective removal of PLA side chains under alkaline conditions generates nanoporous P3HT structures that can be tuned by manipulating molecular design of the bottlebrush scaffold, which is affected by molecular weight and grafting density of the side chains, and their sequence. Furthermore, the ability to exploit the unusual architecture of bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a useful way to design templates for optoelectronic applications or membranes for separations.« less

Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of a tunable molecular bottlebrush scaffold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Suk-kyun; Carrillo, Jan-Michael Y.; Keum, Jong K.

The ability to widely tune the design of macromolecular bottlebrushes provides access to self-assembled nanostructures formed by microphase segregation in melt, thin film and solution that depart from structures adopted by simple linear copolymers. A series of random bottlebrush copolymers containing poly(3-hexylthiophene) (P3HT) and poly(D,L-lactide) (PLA) side chains grafted on a poly(norbornene) backbone were synthesized via ring-opening metathesis polymerization (ROMP) using the grafting through approach. P3HT side chains induce a physical aggregation of the bottlebrush copolymers upon solvent removal by vacuum drying, primarily driven by attractive π–π interactions; however, the amount of aggregation can be controlled by adjusting side chainmore » composition or by adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular dynamics simulations reveal that linear P3HT chains preferentially associate with P3HT side chains of bottlebrush copolymers, which tends to reduce the aggregation. The nanoscale morphology of microphase segregated thin films created by casting P3HT–PLA random bottlebrush copolymers is highly dependent on the composition of P3HT and PLA side chains, while domain spacing of nanostructures is mainly determined by the length of the side chains. The selective removal of PLA side chains under alkaline conditions generates nanoporous P3HT structures that can be tuned by manipulating molecular design of the bottlebrush scaffold, which is affected by molecular weight and grafting density of the side chains, and their sequence. Furthermore, the ability to exploit the unusual architecture of bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a useful way to design templates for optoelectronic applications or membranes for separations.« less

Methylation of hemoglobin to enhance flocculant performance

USDA-ARS?s Scientific Manuscript database

An inexpensive bioflocculant, bovine hemoglobin (Hb), has been covalently modified through methylation of the side chain carboxyl groups of aspartic and glutamic acid residues to improve its flocculation activity. Potentiometric titration of the recovered products showed approximately 28% degree of ...

Alkane oxidation with porphyrins and metal complexes thereof having haloalkyl side chains

DOEpatents

Wijesekera, Tilak; Lyons, James E.; Ellis, Jr., Paul E.; Bhinde, Manoj V.

1998-01-01

Transition metal complexes of meso-haloalkylporphyrins, wherein the haloalkyl groups contain 2 to 8 carbon atoms have been found to be highly effective catalysts for oxidation of alkanes and for the decomposition of hydroperoxides.

A protein-dependent side-chain rotamer library.

PubMed

Bhuyan, Md Shariful Islam; Gao, Xin

2011-12-14

Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations.

PubMed

Andrews, Casey T; Campbell, Brady A; Elcock, Adrian H

2017-04-11

Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid side chains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of 20 amino acid side chain analogs interacting simultaneously with both a 70-base-pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid side chains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged side chains, all types of amino acid side chain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic side chains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged side chains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged side chains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

Side chain-side chain interactions of arginine with tyrosine and aspartic acid in Arg/Gly/Tyr-rich domains within plant glycine-rich RNA binding proteins.

PubMed

Kumaki, Yasuhiro; Nitta, Katsutoshi; Hikichi, Kunio; Matsumoto, Takeshi; Matsushima, Norio

2004-07-01

Plant glycine-rich RNA-binding proteins (GRRBPs) contain a glycine-rich region at the C-terminus whose structure is quite unknown. The C-terminal glycine-rich part is interposed with arginine and tyrosine (arginine/glycine/tyrosine (RGY)-rich domain). Comparative sequence analysis of forty-one GRRBPs revealed that the RGY-rich domain contains multiple repeats of Tyr-(Xaa)h-(Arg)k-(Xaa)l, where Xaa is mainly Gly, "k" is 1 or 2, and "h" and "l" range from 0 to 10. Two peptides, 1 (G1G2Y3G4G5G6R7R8D9G10) and 2 (G1G2R3R4D5G6G7Y8G9G10), corresponding to sections of the RGY-rich domain in Zea mays RAB15, were selected for CD and NMR experiments. The CD spectra indicate a unique, positive band near 228 nm in both peptides that has been ascribed to tyrosine residues in ordered structures. The pH titration by NMR revealed that a side chain-side chain interaction, presumably an H-Nepsilon...O=Cgamma hydrogen bonding interaction in the salt bridge, occurs between Arg (i) and Asp (i + 2). 1D GOESY experiments indicated the presence of NOE between the aromatic side chain proton and the arginine side chain proton in the two peptides suggesting strongly that the Arg (i) aromatic side chain interacts directly with the Tyr (i +/- 4 or i +/- 5) side chain.

Sparse networks of directly coupled, polymorphic, and functional side chains in allosteric proteins.

PubMed

Soltan Ghoraie, Laleh; Burkowski, Forbes; Zhu, Mu

2015-03-01

Recent studies have highlighted the role of coupled side-chain fluctuations alone in the allosteric behavior of proteins. Moreover, examination of X-ray crystallography data has recently revealed new information about the prevalence of alternate side-chain conformations (conformational polymorphism), and attempts have been made to uncover the hidden alternate conformations from X-ray data. Hence, new computational approaches are required that consider the polymorphic nature of the side chains, and incorporate the effects of this phenomenon in the study of information transmission and functional interactions of residues in a molecule. These studies can provide a more accurate understanding of the allosteric behavior. In this article, we first present a novel approach to generate an ensemble of conformations and an efficient computational method to extract direct couplings of side chains in allosteric proteins, and provide sparse network representations of the couplings. We take the side-chain conformational polymorphism into account, and show that by studying the intrinsic dynamics of an inactive structure, we are able to construct a network of functionally crucial residues. Second, we show that the proposed method is capable of providing a magnified view of the coupled and conformationally polymorphic residues. This model reveals couplings between the alternate conformations of a coupled residue pair. To the best of our knowledge, this is the first computational method for extracting networks of side chains' alternate conformations. Such networks help in providing a detailed image of side-chain dynamics in functionally important and conformationally polymorphic sites, such as binding and/or allosteric sites. © 2014 Wiley Periodicals, Inc.

Reduction of the 20-Carbonyl Group of C-21 Steroids by Spores of Fusarium solani and Other Microorganisms. I. Side-Chain Degradation, Epoxide Cleavage, and Substrate Specificity

PubMed Central

Plourde, Rosaire; El-Tayeb, Ossama M.; Hafez-Zedan, Hamdallah

1972-01-01

The spores of Fusarium solani reduced the C2-carbonyl group, 1-dehydrogenated ring „A” and cleaved the side chain of 16α, 17α-oxidopregn-4-ene-3, 20-dione (16α, 17α-oxidoprogesterone)(I) to give the following products: 20α-hydroxy-16α, 17α-oxidopregn-4-en-3-one(II); 20α-hydroxy-16α, 17α-oxidopregna-1, 4-dien-3-one(III); 16α-hydroxy-17a-oxa-androsta-1, 4-diene-3, 17-dione (16α-hydroxy-1-dehydrotestololactone)(IV); and 16α, 17β-dihydroxy-androsta-1, 4-dien-3-one (16α-hydroxy-1-dehydrotestosterone)(V). When II was used as a substrate, it was metabolized into III, IV, and V at a slower rate than I. Furthermore, 16α-hydroxy-androst-4-ene-3, 17-dione (16α-hydroxyandrostenedione)(X) was transformed into IV and V. Pregn-4-ene-3, 20-dione (progesterone)(XII) was transformed into androsta-1, 4-diene-3, 17-dione (androstadienedione)(VIII) and 17a-oxa-androsta-1, 4-diene-3, 17-dione (1-dehydrotestololactone)(IX), while 17α-hydroxy-pregn-4-ene-3, 20-dione (17α-hydroxyprogesterone)(VI) was converted into its 1-dehydro analogue (VII) without accumulation of any 20-dihydro compounds. Substrate specificity in the 20-reductase system of F. solani, Cylindrocarpon radicicola, Septomyxa affinis, Bacillus lentus, and three strains of B. sphaericus are demonstrated. The 20-reductase is active only on steroids having the 16α, 17α-oxido, and Δ4-3-keto functions. Evidence of competition between side-chain degrading enzymes and the 20-reductase for the steroid molecule and evidence of side-chain degradation followed by epoxide cleavage (and not the reverse) are presented. A mechanism for the epoxide opening by nongerminating spores of F. solani is postulated. PMID:5021973

Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

PubMed

Armentrout, P B; Yang, Bo; Rodgers, M T

2014-04-24

Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu < Asn < Gln.

Multifunctional Diketopyrrolopyrrole-Based Conjugated Polymers with Perylene Bisimide Side Chains.

PubMed

Li, Cheng; Yu, Changshi; Lai, Wenbin; Liang, Shijie; Jiang, Xudong; Feng, Guitao; Zhang, Jianqi; Xu, Yunhua; Li, Weiwei

2017-11-24

Two conjugated polymers based on diketopyrrolopyrrole (DPP) in the main chain with different content of perylene bisimide (PBI) side chains are developed. The influence of PBI side chain on the photovoltaic performance of these DPP-based conjugated polymers is systematically investigated. This study suggests that the PBI side chains can not only alter the absorption spectrum and energy level but also enhance the crystallinity of conjugated polymers. As a result, such polymers can act as electron donor, electron acceptor, and single-component active layer in organic solar cells. These findings provide a new guideline for the future molecular design of multifunctional conjugated polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE PAGES

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad; ...

2017-02-24

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations.

PubMed

Liu, Fu-Feng; Liu, Zhen; Bai, Shu; Dong, Xiao-Yan; Sun, Yan

2012-04-14

Aggregation of amyloid-β (Aβ) peptides correlates with the pathology of Alzheimer's disease. However, the inter-molecular interactions between Aβ protofibril remain elusive. Herein, molecular mechanics Poisson-Boltzmann surface area analysis based on all-atom molecular dynamics simulations was performed to study the inter-molecular interactions in Aβ(17-42) protofibril. It is found that the nonpolar interactions are the important forces to stabilize the Aβ(17-42) protofibril, while electrostatic interactions play a minor role. Through free energy decomposition, 18 residues of the Aβ(17-42) are identified to provide interaction energy lower than -2.5 kcal/mol. The nonpolar interactions are mainly provided by the main chain of the peptide and the side chains of nine hydrophobic residues (Leu17, Phe19, Phe20, Leu32, Leu34, Met35, Val36, Val40, and Ile41). However, the electrostatic interactions are mainly supplied by the main chains of six hydrophobic residues (Phe19, Phe20, Val24, Met35, Val36, and Val40) and the side chains of the charged residues (Glu22, Asp23, and Lys28). In the electrostatic interactions, the overwhelming majority of hydrogen bonds involve the main chains of Aβ as well as the guanidinium group of the charged side chain of Lys28. The work has thus elucidated the molecular mechanism of the inter-molecular interactions between Aβ monomers in Aβ(17-42) protofibril, and the findings are considered critical for exploring effective agents for the inhibition of Aβ aggregation.

Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations

NASA Astrophysics Data System (ADS)

Liu, Fu-Feng; Liu, Zhen; Bai, Shu; Dong, Xiao-Yan; Sun, Yan

2012-04-01

Aggregation of amyloid-β (Aβ) peptides correlates with the pathology of Alzheimer's disease. However, the inter-molecular interactions between Aβ protofibril remain elusive. Herein, molecular mechanics Poisson-Boltzmann surface area analysis based on all-atom molecular dynamics simulations was performed to study the inter-molecular interactions in Aβ17-42 protofibril. It is found that the nonpolar interactions are the important forces to stabilize the Aβ17-42 protofibril, while electrostatic interactions play a minor role. Through free energy decomposition, 18 residues of the Aβ17-42 are identified to provide interaction energy lower than -2.5 kcal/mol. The nonpolar interactions are mainly provided by the main chain of the peptide and the side chains of nine hydrophobic residues (Leu17, Phe19, Phe20, Leu32, Leu34, Met35, Val36, Val40, and Ile41). However, the electrostatic interactions are mainly supplied by the main chains of six hydrophobic residues (Phe19, Phe20, Val24, Met35, Val36, and Val40) and the side chains of the charged residues (Glu22, Asp23, and Lys28). In the electrostatic interactions, the overwhelming majority of hydrogen bonds involve the main chains of Aβ as well as the guanidinium group of the charged side chain of Lys28. The work has thus elucidated the molecular mechanism of the inter-molecular interactions between Aβ monomers in Aβ17-42 protofibril, and the findings are considered critical for exploring effective agents for the inhibition of Aβ aggregation.

Hydrophilic Solvation Dominates the Terahertz Fingerprint of Amino Acids in Water.

PubMed

Esser, Alexander; Forbert, Harald; Sebastiani, Federico; Schwaab, Gerhard; Havenith, Martina; Marx, Dominik

2018-02-01

Spectroscopy in the terahertz frequency regime is a sensitive tool to probe solvation-induced effects in aqueous solutions. Yet, a systematic understanding of spectral lineshapes as a result of distinct solvation contributions remains terra incognita. We demonstrate that modularization of amino acids in terms of functional groups allows us to compute their distinct contributions to the total terahertz response. Introducing the molecular cross-correlation analysis method provides unique access to these site-specific contributions. Equivalent groups in different amino acids lead to look-alike spectral contributions, whereas side chains cause characteristic but additive complexities. Specifically, hydrophilic solvation of the zwitterionic groups in valine and glycine leads to similar terahertz responses which are fully decoupled from the side chain. The terahertz response due to H-bonding within the large hydrophobic solvation shell of valine turns out to be nearly indistinguishable from that in bulk water in direct comparison to the changes imposed by the charged functional groups that form strong H-bonds with their hydration shells. Thus, the hydrophilic groups and their solvation shells dominate the terahertz absorption difference, while on the same intensity scale, the influence of hydrophobic water can be neglected.

Compensation Effect in Electrical Conduction Process: Effect of Substituent Group

NASA Astrophysics Data System (ADS)

Mitra, Bani; Misra, T. N.

1987-05-01

The semiconductive properties of Vitamin A acid (Retinoic Acid), a long chain conjugated polyene, were studied as a function of the adsorption of different vapours. A compensation effect was observed in the electrical conduction process; unlike that in Vitamin A alcohol and Vitamin A acetate the compensation temperature was observed on the lower side of the experimental temperature (T0≈285 K). It is concluded that the terminal \\diagdown\\diagupC=0 group conjugated to the polyene chain plays an important role in the manifestation of the compensation effect. Various conduction parameters have been evaluated.

Ionizable side chains at catalytic active sites of enzymes.

PubMed

Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

2012-05-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

Rate constants measured for hydrated electron reactions with peptides and proteins

NASA Technical Reports Server (NTRS)

Braams, R.

1968-01-01

Effects of ionizing radiation on the amino acids of proteins and the reactivity of the protonated amino group depends upon the pK subscript a of the group. Estimates of the rate constants for reactions involving the amino acid side chains are presented. These rate constants gave an approximate rate constant for three different protein molecules.

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

Water-Soluble Polyphosphazenes and Their Hydrogels

DTIC Science & Technology

1994-05-18

side groups, such as -OH, -COONa, -NH2, -NHCH3, -SO3", or -C=O, or amphiphilic units such as -OCH2CH20-, etc. High concentrations of hydrophilic side...soluble polymers since it allows a high degree of utilization of molecular design and either extensive or subtle structural manipulation. The third...advantages for development as water-soluble polymers or hydrogels. The backbone is hydrophilic, the chain structure has a high 3 degree of flexibility, and

Structure and Reaction Mechanism of Basil Eugenol Synthase

PubMed Central

Louie, Gordon V.; Baiga, Thomas J.; Bowman, Marianne E.; Koeduka, Takao; Taylor, John H.; Spassova, Snejina M.; Pichersky, Eran; Noel, Joseph P.

2007-01-01

Phenylpropenes, a large group of plant volatile compounds that serve in multiple roles in defense and pollinator attraction, contain a propenyl side chain. Eugenol synthase (EGS) catalyzes the reductive displacement of acetate from the propenyl side chain of the substrate coniferyl acetate to produce the allyl-phenylpropene eugenol. We report here the structure determination of EGS from basil (Ocimum basilicum) by protein x-ray crystallography. EGS is structurally related to the short-chain dehydrogenase/reductases (SDRs), and in particular, enzymes in the isoflavone-reductase-like subfamily. The structure of a ternary complex of EGS bound to the cofactor NADP(H) and a mixed competitive inhibitor EMDF ((7S,8S)-ethyl (7,8-methylene)-dihydroferulate) provides a detailed view of the binding interactions within the EGS active site and a starting point for mutagenic examination of the unusual reductive mechanism of EGS. The key interactions between EMDF and the EGS-holoenzyme include stacking of the phenyl ring of EMDF against the cofactor's nicotinamide ring and a water-mediated hydrogen-bonding interaction between the EMDF 4-hydroxy group and the side-chain amino moiety of a conserved lysine residue, Lys132. The C4 carbon of nicotinamide resides immediately adjacent to the site of hydride addition, the C7 carbon of cinnamyl acetate substrates. The inhibitor-bound EGS structure suggests a two-step reaction mechanism involving the formation of a quinone-methide prior to reduction. The formation of this intermediate is promoted by a hydrogen-bonding network that favors deprotonation of the substrate's 4-hydroxyl group and disfavors binding of the acetate moiety, akin to a push-pull catalytic mechanism. Notably, the catalytic involvement in EGS of the conserved Lys132 in preparing the phenolic substrate for quinone methide formation through the proton-relay network appears to be an adaptation of the analogous role in hydrogen bonding played by the equivalent lysine residue in other enzymes of the SDR family. PMID:17912370

A new approach to the side chain formation of 24-alkyl-22-hydroxy steroids: application to the preparation of early brassinolide biosynthetic precursors.

PubMed

Hurski, Alaksiej L; Zhabinskii, Vladimir N; Khripach, Vladimir A

2012-06-01

A new synthetic route to 22S-hydroxy-24R-methyl steroids has been developed and applied for the preparation of cathasterone, (22S)-hydroxycampesterol, and 6-deoxocathasterone, which are precursors in the early stages of the biosynthesis of brassinolide. The construction of the steroid side chain with the correct stereochemistry at C-24 is based on the use of Claisen rearrangement. The introduction of the 22-hydroxyl group has been achieved by epoxidation of the Δ(22)-double bond, nucleophilic opening of the intermediate mesyl epoxide with sodium sulfide, and desulfurization of the formed tetrahydrothiophenes with Raney nickel. Copyright © 2012 Elsevier Inc. All rights reserved.

Crystal structure of the 28 kDa glutathione S-transferase from Schistosoma haematobium.

PubMed

Johnson, Kenneth A; Angelucci, Francesco; Bellelli, Andrea; Hervé, Maxime; Fontaine, Josette; Tsernoglou, Demetrious; Capron, André; Trottein, François; Brunori, Maurizio

2003-09-02

Schistomiasis is a debilitating parasitic disease which affects 200 million people, causing life-threatening complications in 10% of the patients. This paper reports the crystal structure of the Schistosoma haematobium 28 kDa glutathione S-transferase, a multifunctional enzyme involved in host-parasite interactions and presently considered as a promising vaccine candidate against schistosomiasis. The structures of the GSH-free enzyme, as well as the partially (approximately 40%) and almost fully (approximately 80%) GSH-saturated enzyme, exhibit a unique feature, absent in previous GST structures, concerning the crucial and invariant Tyr10 side chain which occupies two alternative positions. The canonical conformer, which allows an H-bond to be formed between the side chain hydroxyl group and the activated thiolate of GSH, is somewhat less than 50% occupied. The new conformer, with the phenoxyl ring on the opposite side of the mobile loop connecting strand 1 and helix 1, is stabilized by a polar interaction with the guanidinium group of the conserved Arg21 side chain. The presence of two conformers of Tyr10 may provide a clue about clarifying the multiple catalytic functions of Sh28GST and might prove to be relevant for the design of specific antischistosomal drugs. The K(d) for GSH binding was determined by equilibrium fluorescence titrations to be approximately 3 microM and by stopped-flow rapid mixing experiments to be approximately 9 microM. The relatively tight binding of GSH by Sh28GST explains the residually bound GSH in the crystal and supports a possible role of GSH as a tightly bound cofactor involved in the catalytic mechanism for prostaglandin D(2) synthase activity.

RP-HPLC method using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate incorporated with normalization technique in principal component analysis to differentiate the bovine, porcine and fish gelatins.

PubMed

Azilawati, M I; Hashim, D M; Jamilah, B; Amin, I

2015-04-01

The amino acid compositions of bovine, porcine and fish gelatin were determined by amino acid analysis using 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate as derivatization reagent. Sixteen amino acids were identified with similar spectral chromatograms. Data pre-treatment via centering and transformation of data by normalization were performed to provide data that are more suitable for analysis and easier to be interpreted. Principal component analysis (PCA) transformed the original data matrix into a number of principal components (PCs). Three principal components (PCs) described 96.5% of the total variance, and 2 PCs (91%) explained the highest variances. The PCA model demonstrated the relationships among amino acids in the correlation loadings plot to the group of gelatins in the scores plot. Fish gelatin was correlated to threonine, serine and methionine on the positive side of PC1; bovine gelatin was correlated to the non-polar side chains amino acids that were proline, hydroxyproline, leucine, isoleucine and valine on the negative side of PC1 and porcine gelatin was correlated to the polar side chains amino acids that were aspartate, glutamic acid, lysine and tyrosine on the negative side of PC2. Verification on the database using 12 samples from commercial products gelatin-based had confirmed the grouping patterns and the variables correlations. Therefore, this quantitative method is very useful as a screening method to determine gelatin from various sources. Copyright © 2014 Elsevier Ltd. All rights reserved.

The self-assembly of redox active peptides: Synthesis and electrochemical capacitive behavior.

PubMed

Piccoli, Julia P; Santos, Adriano; Santos-Filho, Norival A; Lorenzón, Esteban N; Cilli, Eduardo M; Bueno, Paulo R

2016-05-01

The present work reports on the synthesis of a redox-tagged peptide with self-assembling capability aiming applications in electrochemically active capacitive surfaces (associated with the presence of the redox centers) generally useful in electroanalytical applications. Peptide containing ferrocene (fc) molecular (redox) group (Ac-Cys-Ile-Ile-Lys(fc)-Ile-Ile-COOH) was thus synthesized by solid phase peptide synthesis (SPPS). To obtain the electrochemically active capacitive interface, the side chain of the cysteine was covalently bound to the gold electrode (sulfur group) and the side chain of Lys was used to attach the ferrocene in the peptide chain. After obtaining the purified redox-tagged peptide, the self-assembly and redox capability was characterized by cyclic voltammetry (CV) and electrochemical impedance-based capacitance spectroscopy techniques. The obtained results confirmed that the redox-tagged peptide was successfully attached by forming an electroactive self-assembled monolayer onto gold electrode. The design of redox active self-assembly ferrocene-tagged peptide is predictably useful in the development of biosensor devices precisely to detect, in a label-free platform, those biomarkers of clinical relevance. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 357-367, 2016. © 2016 Wiley Periodicals, Inc.

Fragmentation pathways of 2-substituted pyrrole derivatives using electrospray ionization ion trap and electrospray ionization quadrupole time-of-flight mass spectrometry.

PubMed

Liang, Xianrui; Guo, Zili; Yu, Chuanming

2013-10-30

Pyrrole derivatives are of considerable importance and are present in a wide range of natural products and used extensively in drug discovery. Fragmentation pathway studies play an important role in the structural identification of pyrrole derivatives. As a part of our ongoing work on heterocycles, fragmentation pathways of 2-substituted pyrrole derivatives were investigated by mass spectrometry (MS). Twelve pyrrole derivatives were synthesized and analyzed. Low-resolution fragmentation ions of all the compounds were generated by ion trap mass spectrometry (ITMS(n) ) with an electrospray ionization (ESI) source in positive mode. Hybrid quadrupole time-of-flight mass spectrometry (QTOFMS) was used to determine the elemental compositions of the resultant product ions. The side-chain substituents at the 2-position influence the fragmentation pathways. Typical losses of H2 O, aldehydes and pyrrole moieties from the [M + H](+) ion are observed for the compounds with side chains bearing aromatic groups at the 2-position of the pyrrole. However, losses of H2 O, alcohols and C3 H6 are the main cleavage pathways for compounds 6 and 12 with nonphenyl-substituted side chains at the 2-position. Typical fragmentation mechanisms of 2-substituted pyrrole derivatives are proposed and elucidated based on the observations of ITMS(n) and QTOFMS spectra. The results showed that the fragmentation pathways were remarkably influenced by the side-chain substituents at the 2-position of pyrrole. This investigation should have value in the structural identification of this series of molecules or compounds with similar structures. Copyright © 2013 John Wiley & Sons, Ltd.

Conformation-Specific IR and UV Spectroscopy of the Amino Acid Glutamine: Amide-Stacking and Hydrogen Bonding in AN Important Residue in Neurodegenerative Diseases

NASA Astrophysics Data System (ADS)

Walsh, Patrick S.; Dean, Jacob C.; Zwier, Timothy S.

2014-06-01

Glutamine plays an important role in several neurodegenerative diseases including Huntington's disease (HD) and Alzheimer's disease (AD). An intriguing aspect of the structure of glutamine is its incorporation of an amide group in its side chain, thereby opening up the possibility of forming amide-amide H-bonds between the peptide backbone and side chain. In this study the conformational preferences of two capped gluatamines Z(carboxybenzyl)-Glutamine-X (X=OH, NHMe) are studied under jet-cooled conditions in the gas phase in order to unlock the intrinsic structural motifs that are favored by this flexible sidechain. Conformational assignments are made by comparing the hydride stretch ( 3100-3700 cm-1) and amide I and II ( 1400-1800 cm-1) resonant ion-dip infrared spectra with predictions from harmonic frequency calculations. Assigned structures will be compared to previously published results on both natural and unnatural residues. Particular emphasis will be placed on the comparison between glutamine and unconstrained γ-peptides due to the similar three-carbon spacing between backbone and side chain in glutamine to the backbone spacing in γ-peptides. The ability of the glutamine side-chain to form amide stacked conformations will be a main focus, along with the prevalence of extended backbone type structures. W. H. James, III, C W. Müller, E. G. Buchanan, M. G. D. Nix, L. Guo, L. Roskop, M. S. Gordon, L. V. Slipchenko, S. H. Gellman, and T. S. Zwier, J. Am. Chem. Soc., 2009, 131(40), 14243-14245.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Chunya; Skelton, Adam A.; Chen, Mingjun

Here the binding of a negatively charged residue, aspartic acid (Asp) in tripeptide arginine-glycine-aspartic acid, onto a negatively charged hydroxylated rutile (110) surface in aqueous solution, containing divalent (Mg 2+, Ca 2+, or Sr 2+) or monovalent (Na +, K +, or Rb +) cations, was studied by molecular dynamics (MD) simulations. The results indicate that ionic radii and charges will significantly affect the hydration, adsorption geometry, and distance of cations from the rutile surface, thereby regulating the Asp/rutile binding mode. The adsorption strength of monovalent cations on the rutile surface in the order Na + > K + >more » Rb + shows a “reverse” lyotropic trend, while the divalent cations on the same surface exhibit a “regular” lyotropic behavior with decreasing crystallographic radii (the adsorption strength of divalent cations: Sr 2+ > Ca 2+ > Mg 2+). The Asp side chain in NaCl, KCl, and RbCl solutions remains stably H-bonded to the surface hydroxyls and the inner-sphere adsorbed compensating monovalent cations act as a bridge between the COO – group and the rutile, helping to “trap” the negatively charged Asp side chain on the negatively charged surface. In contrast, the mediating divalent cations actively participate in linking the COO– group to the rutile surface; thus the Asp side chain can remain stably on the rutile (110) surface, even if it is not involved in any hydrogen bonds with the surface hydroxyls. Inner- and outer-sphere geometries are all possible mediation modes for divalent cations in bridging the peptide to the rutile surface.« less

Alkane oxidation with porphyrins and metal complexes thereof having haloalkyl side chains

DOEpatents

Wijesekera, T.; Lyons, J.E.; Ellis, P.E. Jr.; Bhinde, M.V.

1998-06-23

Transition metal complexes of meso-haloalkylporphyrins are disclosed, wherein the haloalkyl groups contain 2 to 8 carbon atoms have been found to be highly effective catalysts for oxidation of alkanes and for the decomposition of hydroperoxides. 7 figs.

A combinatorial approach to protein docking with flexible side chains.

PubMed

Althaus, Ernst; Kohlbacher, Oliver; Lenhof, Hans-Peter; Müller, Peter

2002-01-01

Rigid-body docking approaches are not sufficient to predict the structure of a protein complex from the unbound (native) structures of the two proteins. Accounting for side chain flexibility is an important step towards fully flexible protein docking. This work describes an approach that allows conformational flexibility for the side chains while keeping the protein backbone rigid. Starting from candidates created by a rigid-docking algorithm, we demangle the side chains of the docking site, thus creating reasonable approximations of the true complex structure. These structures are ranked with respect to the binding free energy. We present two new techniques for side chain demangling. Both approaches are based on a discrete representation of the side chain conformational space by the use of a rotamer library. This leads to a combinatorial optimization problem. For the solution of this problem, we propose a fast heuristic approach and an exact, albeit slower, method that uses branch-and-cut techniques. As a test set, we use the unbound structures of three proteases and the corresponding protein inhibitors. For each of the examples, the highest-ranking conformation produced was a good approximation of the true complex structure.

Gas Phase Dissociation Behavior of Acyl-Arginine Peptides.

PubMed

McGee, William M; McLuckey, Scott A

2013-11-15

The gas phase dissociation behavior of peptides containing acyl-arginine residues is investigated. These acylations are generated via a combination of ion/ion reactions between arginine-containing peptides and N -hydroxysuccinimide (NHS) esters and subsequent tandem mass spectrometry (MS/MS). Three main dissociation pathways of acylated arginine, labeled Paths 1-3, have been identified and are dependent on the acyl groups. Path 1 involves the acyl-arginine undergoing deguanidination, resulting in the loss of the acyl group and dissociation of the guanidine to generate an ornithine residue. This pathway generates selective cleavage sites based on the recently discussed "ornithine effect". Path 2 involves the coordinated losses of H 2 O and NH 3 from the acyl-arginine side chain while maintaining the acylation. We propose that Path 2 is initiated via cyclization of the δ-nitrogen of arginine and the C-terminal carbonyl carbon, resulting in rapid rearrangement from the acyl-arginine side chain and the neutral losses. Path 3 occurs when the acyl group contains α-hydrogens and is observed as a rearrangement to regenerate unmodified arginine while the acylation is lost as a ketene.

Improved packing of protein side chains with parallel ant colonies.

PubMed

Quan, Lijun; Lü, Qiang; Li, Haiou; Xia, Xiaoyan; Wu, Hongjie

2014-01-01

The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms.

Versatile On-Resin Synthesis of High Mannose Glycosylated Asparagine with Functional Handles

PubMed Central

Chen, Rui; Pawlicki, Mark A.; Tolbert, Thomas J.

2013-01-01

Here we present a synthetic route for solid phase synthesis of N-linked glycoconjugates containing high mannose oligosaccharides which allows the incorporation of useful functional handles on the N-terminus of asparagine. In this strategy, the C-terminus of an Fmoc protected aspartic acid residue is first attached to a solid phase support. The side chain of aspartic acid is protected by a 2-phenylisopropyl protecting group, which allows selective deprotection for the introduction of glycosylation. By using a convergent on-resin glycosylamine coupling strategy, an N-glycosidic linkage is successfully formed on the free side chain of the resin bound aspartic acid with a large high mannose oligosaccharide, Man8GlcNAc2, to yield N-linked high mannose glycosylated asparagine. The use of on-resin glycosylamine coupling provides excellent glycosylation yield, can be applied to couple other types of oligosaccharides, and also makes it possible to recover excess oligosaccharides conveniently after the on-resin coupling reaction. Useful functional handles including an alkene (p-vinylbenzoic acid), an alkyne (4-pentynoic acid), biotin, and 5-carboxyfluorescein are then conjugated onto the N-terminal amine of asparagine on-resin after the removal of the Fmoc protecting group. In this way, useful functional handles are introduced onto the glycosylated asparagine while maintaining the structural integrity of the reducing end of the oligosaccharide. The asparagine side chain also serves as a linker between the glycan and the functional group and preserves the native presentation of N-linked glycan which may aid in biochemical and structural studies. As an example of a biochemical study using functionalized high mannose glycosylated asparagine, a fluorescence polarization assay has been utilized to study the binding of the lectin Concanavalin A (ConA) using 5-carboxyfluorescein labeled high mannose glycosylated asparagine. PMID:24326091

Sterols of Saccharomyces cerevisiae erg6 Knockout Mutant Expressing the Pneumocystis carinii S-Adenosylmethionine:Sterol C-24 Methyltransferase.

PubMed

Kaneshiro, Edna S; Johnston, Laura Q; Nkinin, Stephenson W; Romero, Becky I; Giner, José-Luis

2015-01-01

The AIDS-associated lung pathogen Pneumocystis is classified as a fungus although Pneumocystis has several distinct features such as the absence of ergosterol, the major sterol of most fungi. The Pneumocystis carinii S-adenosylmethionine:sterol C24-methyltransferase (SAM:SMT) enzyme, coded by the erg6 gene, transfers either one or two methyl groups to the C-24 position of the sterol side chain producing both C28 and C29 24-alkylsterols in approximately the same proportions, whereas most fungal SAM:SMT transfer only one methyl group to the side chain. The sterol compositions of wild-type Sacchromyces cerevisiae, the erg6 knockout mutant (Δerg6), and Δerg6 expressing the P. carinii or the S. cerevisiae erg6 gene were analyzed by a variety of chromatographic and spectroscopic procedures to examine functional complementation in the yeast expression system. Detailed sterol analyses were obtained using high performance liquid chromatography and proton nuclear magnetic resonance spectroscopy ((1)H-NMR). The P. carinii SAM:SMT in the Δerg6 restored its ability to produce the C28 sterol ergosterol as the major sterol, and also resulted in low levels of C29 sterols. This indicates that while the P. carinii SAM:SMT in the yeast Δerg6 cells was able to transfer a second methyl group to the side chain, the action of Δ(24(28)) -sterol reductase (coded by the erg4 gene) in the yeast cells prevented the formation and accumulation of as many C29 sterols as that found in P. carinii. © 2014 The Author(s) Journal of Eukaryotic Microbiology © 2014 International Society of Protistologists.

Sterols of Saccharomyces cerevisiae erg6 Knockout Mutant Expressing the Pneumocystis carinii S-Adenosylmethionine:Sterol C-24 Methyltransferase (SAM:SMT)

PubMed Central

Kaneshiro, Edna S.; Johnston, Laura Q.; Nkinin, Stephenson W.; Romero, Becky I.; Giner, José-Luis

2014-01-01

The AIDS-associated lung pathogen Pneumocystis is classified as a fungus although Pneumocystis has several distinct features such as the absence of ergosterol, the major sterol of most fungi. The P. carinii S-adenosylmethionine:sterol C24-methyltransferase (SAM:SMT) enzyme, coded by the erg6 gene, transfers either one or two methyl groups to the C-24 position of the sterol side chain producing both C28 and C29 24-alkylsterols in approximately the same proportions whereas most fungal SAM:SMT transfer only one methyl group to the side chain. The sterol compositions of wild type Sacchromyces cerevisiae, the erg6 knockout mutant (Δerg6), and Δerg6 expressing the P. carinii or the S. cerevisiae erg6 gene were analyzed by a variety of chromatographic and spectroscopic procedures to examine functional complementation in the yeast expression system. Detailed sterol analyses were obtained using high performance liquid chromatography (HPLC) and proton nuclear magnetic resonance spectroscopy (1H-NMR). The P. carinii SAM:SMT in the Δerg6 restored its ability to produce the C28 sterol ergosterol as the major sterol, and also resulted in low levels of C29 sterols. This indicates that while the P. carinii SAM:SMT in the yeast Δerg6 cells was able to transfer a second methyl group to the side chain, the action of Δ24(28)-sterol reductase (coded by the erg4 gene) in the yeast cells prevented the formation and accumulation of as many C29 sterols as that found in P. carinii. PMID:25230683

22. VIEW LOOKING FORWARD INTO CHAIN LOCKER FROM PORT SIDE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. VIEW LOOKING FORWARD INTO CHAIN LOCKER FROM PORT SIDE ENTRY THROUGH CHAIN LOCKER BULKHEAD. PAWL BITT SHOWN IN FOREGROUND - Pilot Schooner "Alabama", Moored in harbor at Vineyard Haven, Vineyard Haven, Dukes County, MA

Hedgehog Protein Cholesterolysis: A New Therapeutic Target for Advanced Prostate Cancer

DTIC Science & Technology

2016-10-01

research group page, with links to publicationshttp://www.binghamton.edu/chemistry/people/callahan/callahan.html s 5. PARTICIPANTS & OTHER COLLABORATING...which changes the side chain by only a methylene group . All four expressed as soluble proteins in E. coli and exhibited strong FRET signals consistent...Acknowledgements We thank members of the Callahan research group for technical assistance and helpful comments on the manuscript. Special thanks to Dr

Data on synthesis and thermo-mechanical properties of stimuli-responsive rubber materials bearing pendant anthracene groups.

PubMed

Manhart, Jakob; Ayalur-Karunakaran, Santhosh; Radl, Simone; Oesterreicher, Andreas; Moser, Andreas; Ganser, Christian; Teichert, Christian; Pinter, Gerald; Kern, Wolfgang; Griesser, Thomas; Schlögl, Sandra

2016-12-01

The photo-reversible [4πs+4πs] cycloaddition reaction of pendant anthracene moieties represents a convenient strategy to impart wavelength dependent properties into hydrogenated carboxylated nitrile butadiene rubber (HXNBR) networks. The present article provides the 1 H NMR data on the reaction kinetics of the side chain functionalization of HXNBR. 2-(Anthracene-9-yl)oxirane with reactive epoxy groups is covalently attached to the polymer side chain of HXNBR via ring opening reaction between the epoxy and the carboxylic groups. Along with the identification, 1 H NMR data on the quantification of the attached functional groups are shown in dependence on reaction time and concentration of 2-(anthracene-9-yl)oxirane. Changes in the modification yield are reflected in the mechanical properties and DMA data of photo-responsive elastomers are illustrated in dependence on the number of attached anthracene groups. DMA curves over repeated cycles of UV induced crosslinking ( λ >300 nm) and UV induced cleavage ( λ =254 nm) are further depicted, demonstrating the photo-reversibility of the thermo-mechanical properties. Interpretation and discussion of the data are provided in "Design and application of photo-reversible elastomer networks by using the [4πs+4πs] cycloaddition reaction of pendant anthracene groups" (Manhart et al., 2016) [1].

Liquid crystal polymers: evidence of hairpin defects in nematic main chains, comparison with side chain polymers

NASA Astrophysics Data System (ADS)

Li, M. H.; Brûlet, A.; Keller, P.; Cotton, J. P.

1996-09-01

This article describes the conformation of two species of liquid crystalline polymers as revealed by small angle neutron scattering. The results obtained with side chain polymers are recalled. The procedure used to analyze the scattering data of main chains in the nematic phase is reported in this paper. It permits a demonstration of the existence of hairpins. Comparison of both polymer species shows that in the isotropic phase, the two polymers adopt a random coil conformation. In the nematic phase, the conformations are very different; the side chains behave as a melt of penetrable random coils whereas the main chains behave as a nematic phase of non penetrable cylinders.

Differential effects of Phe19 and Phe20 on fibril formation by amyloidogenic peptide A beta 16-22 (Ac-KLVFFAE-NH2).

PubMed

Inouye, Hideyo; Gleason, Katherine A; Zhang, Dong; Decatur, Sean M; Kirschner, Daniel A

2010-08-01

The sequence KLVFFAE (A beta 16-22) in Alzheimer's beta-amyloid is thought to be a core beta-structure that could act as a template for folding other parts of the polypeptide or molecules into fibrillar assemblies rich in beta-sheet. To elucidate the mechanism of the initial folding process, we undertook combined X-ray fiber/powder diffraction and infrared (IR) spectroscopy to analyze lyophilized A beta 16-22 and solubilized/dried peptide containing nitrile probes at F19 and/or F20. Solubilized/dried wild-type (WT) A beta 16-22 and the peptide containing cyanophenylalanine at F19 (19CN) or at F20 (20CN) gave fiber patterns consistent with slab-like beta-crystallites that were cylindrically averaged around the axis parallel to the polypeptide chain direction. The WT and 19CN assemblies showed 30-A period arrays arising from the stacking of the slabs along the peptide chain direction, whereas the 20CN assemblies lacked any such stacking. The electron density projection along the peptide chain direction indicated similar side-chain dispositions for WT and 20CN, but not for 19CN. These X-ray results and modeling imply that in the assembly of WT A beta 16-22 the F19 side chain is localized within the intersheet space and is involved in hydrophobic contact with amino acids across the intersheet space, whereas the F20 side chain localized near the slab surface is less important for the intersheet interaction, but involved in slab stacking. IR observations for the same peptides in dilute solution showed a greater degree of hydrogen bonding for the nitrile groups in 20CN than in 19CN, supporting this interpretation. (c) 2010 Wiley-Liss, Inc.

Investigation of the interfacial reaction between metal and fluorine-contained polyimides

NASA Astrophysics Data System (ADS)

Yang, Ching-Yu; Chen, J. S.; Hsu, S. L. C.

2005-07-01

In this work, thin metal films (Cr and Ta) were deposited on fluorine-contained polyimides, 6FDA-BisAAF, and 6FDA-PPD. The chemical states of the metal/polyimide samples were characterized by using x-ray photoelectron spectroscopy (XPS). XPS analysis reveals that metal-C, C-O, and metal-O bondings are present in metallized 6FDA-BisAAF and 6FDA-PPD. C-F bonds are observed in bare 6FDA-BisAAF and 6FDA-PPD however, they are not seen in the metallized samples. Disappearance of the C-F bonding is attributed to the disruption of CF3 side groups from the main chains of 6FDA-BisAAF and 6FDA-PPD when the chains are exposed to the plasma during the metal deposition. Nevertheless, the disruption of CF3 side groups also creates sites for the formation of metal-C or C-O bondings, which provide a positive adhesion strength at the metal/polyimide interface, as revealed by the tape test.

Molecular engineering of fracture energy dissipating sacrificial bonds into cellulose nanocrystal nanocomposites.

PubMed

McKee, Jason R; Huokuna, Johannes; Martikainen, Lahja; Karesoja, Mikko; Nykänen, Antti; Kontturi, Eero; Tenhu, Heikki; Ruokolainen, Janne; Ikkala, Olli

2014-05-12

Even though nanocomposites have provided a plethora of routes to increase stiffness and strength, achieving increased toughness with suppressed catastrophic crack growth has remained more challenging. Inspired by the concepts of mechanically excellent natural nanomaterials, one-component nanocomposites were fabricated involving reinforcing colloidal nanorod cores with polymeric grafts containing supramolecular binding units. The concept is based on mechanically strong native cellulose nanocrystals (CNC) grafted with glassy polymethacrylate polymers, with side chains that contain 2-ureido-4[1H]-pyrimidone (UPy) pendant groups. The interdigitation of the grafts and the ensuing UPy hydrogen bonds bind the nanocomposite network together. Under stress, UPy groups act as sacrificial bonds: simultaneously providing adhesion between the CNCs while allowing them to first orient and then gradually slide past each other, thus dissipating fracture energy. We propose that this architecture involving supramolecular binding units within side chains of polymer grafts attached to colloidal reinforcements opens generic approaches for tough nanocomposites. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Terminal alkenes as versatile chemical reporter groups for metabolic oligosaccharide engineering.

PubMed

Späte, Anne-Katrin; Schart, Verena F; Schöllkopf, Sophie; Niederwieser, Andrea; Wittmann, Valentin

2014-12-08

The Diels-Alder reaction with inverse electron demand (DAinv reaction) of 1,2,4,5-tetrazines with electron rich or strained alkenes was proven to be a bioorthogonal ligation reaction that proceeds fast and with high yields. An important application of the DAinv reaction is metabolic oligosaccharide engineering (MOE) which allows the visualization of glycoconjugates in living cells. In this approach, a sugar derivative bearing a chemical reporter group is metabolically incorporated into cellular glycoconjugates and subsequently derivatized with a probe by means of a bioorthogonal ligation reaction. Here, we investigated a series of new mannosamine and glucosamine derivatives with carbamate-linked side chains of varying length terminated by alkene groups and their suitability for labeling cell-surface glycans. Kinetic investigations showed that the reactivity of the alkenes in DAinv reactions increases with growing chain length. When applied to MOE, one of the compounds, peracetylated N-butenyloxycarbonylmannosamine, was especially well suited for labeling cell-surface glycans. Obviously, the length of its side chain represents the optimal balance between incorporation efficiency and speed of the labeling reaction. Sialidase treatment of the cells before the bioorthogonal labeling reaction showed that this sugar derivative is attached to the glycans in form of the corresponding sialic acid derivative and not epimerized to another hexosamine derivative to a considerable extent. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser amplifier chain

DOEpatents

Hackel, Richard P.

1992-01-01

A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain.

Linear rheology and structure of molecular bottlebrushes with short side chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Barrón, Carlos R., E-mail: carlos.r.lopez-barron@exxonmobil.com; Brant, Patrick; Crowther, Donna J.

We investigate the microstructure and linear viscoelasticity of model molecular bottlebrushes (BBs) using rheological and small-angle X-ray and neutron scattering measurements. Our polymers have short atactic polypropylene (aPP) side chains of molecular weight ranging from 119 g/mol to 259 g/mol and narrow molecular weight distribution (M{sub w}/M{sub n} 1.02–1.05). The side chain molecular weights are a small fraction of the entanglement molecular weight of the corresponding linear polymer (M{sub e,aPP}= 7.05 kg/mol), and as such, they are unentangled. The morphology of the aPP BBs is characterized as semiflexible thick chains with small side chain interdigitation. Their dynamic master curves, obtained by time-temperature superposition,more » reveal two sequential relaxation processes corresponding to the segmental relaxation and the relaxation of the BB backbone. Due to the short length of the side chains, their fast relaxation could not be distinguished from the glassy relaxation. The fractional free volume is an increasing function of the side chain length (N{sub SC}). Therefore, the glassy behavior of these polymers as well as their molecular friction and dynamic properties are influenced by their N{sub SC} values. The apparent flow activation energies are a decreasing function of N{sub SC}, and their values explain the differences in zero-shear viscosity measured at different temperatures.« less

Use of side-chain incompatibility for tailoring long-range p/n heterojunctions: photoconductive nanofibers formed by self-assembly of an amphiphilic donor-acceptor dyad consisting of oligothiophene and perylenediimide.

PubMed

Li, Wei-Shi; Saeki, Akinori; Yamamoto, Yohei; Fukushima, Takanori; Seki, Shu; Ishii, Noriyuki; Kato, Kenichi; Takata, Masaki; Aida, Takuzo

2010-07-05

To tailor organic p/n heterojunctions with molecular-level precision, a rational design strategy using side-chain incompatibility of a covalently connected donor-acceptor (D-A) dyad has been successfully carried out. An oligothiophene-perylenediimide dyad, when modified with triethylene glycol side chains at one terminus and dodecyl side chains at the other (2(Amphi)), self-assembles into nanofibers with a long-range D/A heterojunction. In contrast, when the dyad is modified with dodecyl side chains at both termini (2(Lipo)), ill-defined microfibers result. In steady-state measurements using microgap electrodes, a cast film of the nanofiber of 2(Amphi) displays far better photoconducting properties than that of the microfiber of 2(Lipo). Flash-photolysis time-resolved microwave conductivity measurements, in conjunction with transient absorption spectroscopy, clearly indicate that the nanofiber of 2(Amphi) intrinsically allows for better carrier generation and transport properties than the microfibrous assembly of 2(Lipo).

Synthesis of new C-25 and C-26 steroidal acids as potential ligands of the nuclear receptors DAF-12, LXR and GR.

PubMed

Dansey, María V; Del Fueyo, María C; Veleiro, Adriana S; Di Chenna, Pablo H

2017-05-01

A new methodology to obtain C-25 and C-26 steroidal acids starting from pregnenolone is described. Construction of the side chain was achieved by applying the Mukaiyama aldol reaction with a non-hydrolytic work-up to isolate the trapped silyl enol ether with higher yields. Using this methodology we synthesized three new steroidal acids as potential ligands of DAF-12, Liver X and Glucocorticoid nuclear receptors and studied their activity in reporter gene assays. Our results show that replacement of the 21-CH 3 by a 20-keto group in the side chains of the cholestane scaffold of DAF-12 or Liver X receptors ligands causes the loss of the activity. Copyright © 2017 Elsevier Inc. All rights reserved.

A Modular PV System Using Chain-Link-Type Multilevel Converter

NASA Astrophysics Data System (ADS)

Hatano, Nobuhiko; Ise, Toshifumi

This paper presents a modular photovoltaic system (MPVS) that uses a chain-link-type multilevel converter (CLMC). In large-scale PV generating systems, the DC power supply is generally composed of a large number of PV panels. Hence, losses are caused by differences in the maximum power point at each PV panel. An MPVS has been proposed to address the above mentioned problem. It helps improve the photoelectric conversion efficiency by applying maximum power point tracking (MPPT) control to each group of PV panels. In addition, if a CLMC is used in an MPVS, a high voltage can be output from the AC side and transmission losses can be decreased. However, with this circuit configuration, the current output from the AC side may be unbalanced. Therefore, we propose a method to output balanced current from the AC side, even if the output of the DC power supply is unbalanced. The validity of the proposed method is examined by digital simulation.

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

NASA Astrophysics Data System (ADS)

Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.

1989-06-01

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.

Role of Side Chains in β-Sheet Self-Assembly into Peptide Fibrils. IR and VCD Spectroscopic Studies of Glutamic Acid-Containing Peptides.

PubMed

Tobias, Fernando; Keiderling, Timothy A

2016-05-10

Poly(glutamic acid) at low pH self-assembles after incubation at higher temperature into fibrils composed of antiparallel sheets that are stacked in a β2-type structure whose amide carbonyls have bifurcated H-bonds involving the side chains from the next sheet. Oligomers of Glu can also form such structures, and isotope labeling has provided insight into their out-of-register antiparallel structure [ Biomacromolecules 2013 , 14 , 3880 - 3891 ]. In this paper we report IR and VCD spectra and transmission electron micrograph (TEM) images for a series of alternately sequenced oligomers, Lys-(Aaa-Glu)5-Lys-NH2, where Aaa was varied over a variety of polar, aliphatic, or aromatic residues. Their spectral and TEM data show that these oligopeptides self-assemble into different structures, both local and morphological, that are dependent on both the nature of the Aaa side chains and growth conditions employed. Such alternate peptides substituted with small or polar residues, Ala and Thr, do not yield fibrils; but with β-branched aliphatic residues, Val and Ile, that could potentially pack with Glu side chains, these oligopeptides do show evidence of β2-stacking. By contrast, for Leu, with longer side chains, only β1-stacking is seen while with even larger Phe side chains, either β-form can be detected separately, depending on preparation conditions. These structures are dependent on high temperature incubation after reducing the pH and in some cases after sonication of initial fibril forms and reincubation. Some of these fibrillar peptides, but not all, show enhanced VCD, which can offer evidence for formation of long, multistrand, often twisted structures. Substitution of Glu with residues having selected side chains yields a variety of morphologies, leading to both β1- and β2-structures, that overall suggests two different packing modes for the hydrophobic side chains depending on size and type.

Role of Rhodobacter sphaeroides photosynthetic reaction center residue M214 in the composition, absorbance properties, and conformations of H(A) and B(A) cofactors.

PubMed

Saer, Rafael G; Hardjasa, Amelia; Rosell, Federico I; Mauk, A Grant; Murphy, Michael E P; Beatty, J Thomas

2013-04-02

In the native reaction center (RC) of Rhodobacter sphaeroides, the side chain of (M)L214 projects orthogonally toward the plane and into the center of the A branch bacteriopheophytin (BPhe) macrocycle. The possibility that this side chain is responsible for the dechelation of the central Mg(2+) of bacteriochlorophyll (BChl) was investigated by replacement of (M)214 with residues possessing small, nonpolar side chains that can neither coordinate nor block access to the central metal ion. The (M)L214 side chain was also replaced with Cys, Gln, and Asn to evaluate further the requirements for assembly of the RC with BChl in the HA pocket. Photoheterotrophic growth studies showed no difference in growth rates of the (M)214 nonpolar mutants at a low light intensity, but the growth of the amide-containing mutants was impaired. The absorbance spectra of purified RCs indicated that although absorbance changes are associated with the nonpolar mutations, the nonpolar mutant RC pigment compositions are the same as in the wild-type protein. Crystal structures of the (M)L214G, (M)L214A, and (M)L214N mutants were determined (determined to 2.2-2.85 Å resolution), confirming the presence of BPhe in the HA pocket and revealing alternative conformations of the phytyl tail of the accessory BChl in the BA site of these nonpolar mutants. Our results demonstrate that (i) BChl is converted to BPhe in a manner independent of the aliphatic side chain length of nonpolar residues replacing (M)214, (ii) BChl replaces BPhe if residue (M)214 has an amide-bearing side chain, (iii) (M)214 side chains containing sulfur are not sufficient to bind BChl in the HA pocket, and (iv) the (M)214 side chain influences the conformation of the phytyl tail of the BA BChl.

NMR (Nuclear Magnetic Resonance) of solid biopolymers

NASA Technical Reports Server (NTRS)

Andrew, E. R.

1983-01-01

It has been possible through the study of proton relaxation in solid proteins and related molecules to identify and characterize the following molecular motions which contribute to relaxation: (1) methyl group reorientation; (2) segmental motion; (3) side chain motion; (4) proline ring puckering; and (5) water molecule reorientation.

Guanidino Groups Greatly Enhance the Action of Antimicrobial Peptidomimetics Against Bacterial Cytoplasmic Membranes

DTIC Science & Technology

2014-05-28

SECURITY CLASSIFICATION OF: Antimicrobial peptides or their synthetic mimics are a promising class of potential new antibiotics. Herein we assess the...effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial ?- peptide ...P.O. Box 12211 Research Triangle Park, NC 27709-2211 Antimicrobial peptidomimetics; Peptide –peptoid chimeras; Guanidinium cation; Bacterial

Nature nurtures the design of new semi-synthetic macrolide antibiotics.

PubMed

Fernandes, Prabhavathi; Martens, Evan; Pereira, David

2017-05-01

Erythromycin and its analogs are used to treat respiratory tract and other infections. The broad use of these antibiotics during the last 5 decades has led to resistance that can range from 20% to over 70% in certain parts of the world. Efforts to find macrolides that were active against macrolide-resistant strains led to the development of erythromycin analogs with alkyl-aryl side chains that mimicked the sugar side chain of 16-membered macrolides, such as tylosin. Further modifications were made to improve the potency of these molecules by removal of the cladinose sugar to obtain a smaller molecule, a modification that was learned from an older macrolide, pikromycin. A keto group was introduced after removal of the cladinose sugar to make the new ketolide subclass. Only one ketolide, telithromycin, received marketing authorization but because of severe adverse events, it is no longer widely used. Failure to identify the structure-relationship responsible for this clinical toxicity led to discontinuation of many ketolides that were in development. One that did complete clinical development, cethromycin, did not meet clinical efficacy criteria and therefore did not receive marketing approval. Work on developing new macrolides was re-initiated after showing that inhibition of nicotinic acetylcholine receptors by the imidazolyl-pyridine moiety on the side chain of telithromycin was likely responsible for the severe adverse events. Solithromycin is a fourth-generation macrolide that has a fluorine at the 2-position, and an alkyl-aryl side chain that is different from telithromycin. Solithromycin interacts at three sites on the bacterial ribosome, has activity against strains resistant to older macrolides (including telithromycin), and is mostly bactericidal. Pharmaceutical scientists involved in the development of macrolide antibiotics have learned from the teachings of Professor Satoshi Omura and progress in this field was not possible without his endeavors.

Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2008-01-01

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid-base properties in alanine-based peptides. Hence, the acid-base properties of three alanine-based peptides: Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2) (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH-metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson-Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.

Steroid hydroxylation by basidiomycete peroxygenases: a combined experimental and computational study.

PubMed

Babot, Esteban D; Del Río, José C; Cañellas, Marina; Sancho, Ferran; Lucas, Fátima; Guallar, Víctor; Kalum, Lisbeth; Lund, Henrik; Gröbe, Glenn; Scheibner, Katrin; Ullrich, René; Hofrichter, Martin; Martínez, Angel T; Gutiérrez, Ana

2015-06-15

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106-118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Steroid Hydroxylation by Basidiomycete Peroxygenases: a Combined Experimental and Computational Study

PubMed Central

Babot, Esteban D.; del Río, José C.; Cañellas, Marina; Sancho, Ferran; Lucas, Fátima; Guallar, Víctor; Kalum, Lisbeth; Lund, Henrik; Gröbe, Glenn; Scheibner, Katrin; Ullrich, René; Hofrichter, Martin; Martínez, Angel T.

2015-01-01

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H2O2 as the only cosubstrate. Two of them are wild-type enzymes from Agrocybe aegerita and Marasmius rotula, and the third one is a recombinant enzyme from Coprinopsis cinerea. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013, http://dx.doi.org/10.1016/j.immuni.2012.11.004). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed. PMID:25862224

Space Survivability of Main-Chain and Side-Chain POSS-Kapton Polyimides

NASA Astrophysics Data System (ADS)

Tomczak, Sandra J.; Wright, Michael E.; Guenthner, Andrew J.; Pettys, Brian J.; Brunsvold, Amy L.; Knight, Casey; Minton, Timothy K.; Vij, Vandana; McGrath, Laura M.; Mabry, Joseph M.

2009-01-01

Kapton® polyimde (PI) is extensively used in solar arrays, spacecraft thermal blankets, and space inflatable structures. Upon exposure to atomic oxygen (AO) in low Earth orbit (LEO), Kapton® is severely degraded. An effective approach to prevent this erosion is chemically bonding polyhedral oligomeric silsesquioxane (POSS) into the polyimide matrix by copolymerization of POSS-diamine with the polyimide monomers. POSS is a silicon and oxygen cage-like structure surrounded by organic groups and can be polymerizable. The copolymerization of POSS provides Si and O in the polymer matrix on the nano level. During POSS polyimide exposure to atomic oxygen, organic material is degraded and a silica passivation layer is formed. This silica layer protects the underlying polymer from further degradation. Ground-based studies and MISSE-1 and MISSE-5 flight results have shown that POSS polyimides are resistant to atomic-oxygen attack in LEO. In fact, 3.5 wt% Si8O11 main-chain POSS polyimide eroded about 2 μm during the 3.9 year flight in LEO, whereas 32 μm of 0 wt% POSS polyimide would have eroded within 4 mos. The atomic-oxygen exposure of main-chain POSS polyimides and new side-chain POSS polyimides has shown that copolymerized POSS imparts similar AO resistance to polyimide materials regardless of POSS monomer structure.

First-second shell interactions in metal binding sites in proteins: a PDB survey and DFT/CDM calculations.

PubMed

Dudev, Todor; Lin, Yen-lin; Dudev, Minko; Lim, Carmay

2003-03-12

The role of the second shell in the process of metal binding and selectivity in metalloproteins has been elucidated by combining Protein Data Bank (PDB) surveys of Mg, Mn, Ca, and Zn binding sites with density functional theory/continuum dielectric methods (DFT/CDM). Peptide backbone groups were found to be the most common second-shell ligand in Mg, Mn, Ca, and Zn binding sites, followed (in decreasing order) by Asp/Glu, Lys/Arg, Asn/Gln, and Ser/Thr side chains. Aromatic oxygen- or nitrogen-containing side chains (Tyr, His, and Trp) and sulfur-containing side chains (Cys and Met) are seldom found in the second coordination layer. The backbone and Asn/Gln side chain are ubiquitous in the metal second coordination layer as their carbonyl oxygen and amide hydrogen can act as a hydrogen-bond acceptor and donor, respectively, and can therefore partner practically every first-shell ligand. The second most common outer-shell ligand, Asp/Glu, predominantly hydrogen bonds to a metal-bound water or Zn-bound histidine and polarizes the H-O or H-N bond. In certain cases, a second-shell Asp/Glu could affect the protonation state of the metal ligand. It could also energetically stabilize a positively charged metal complex more than a neutral ligand such as the backbone and Asn/Gln side chain. As for the first shell, the second shell is predicted to contribute to the metal selectivity of the binding site by discriminating between metal cations of different ionic radii and coordination geometries. The first-shell-second-shell interaction energies decay rapidly with increasing solvent exposure of the metal binding site. They are less favorable but are of the same order of magnitude as compared to the respective metal-first-shell interaction energies. Altogether, the results indicate that the structure and properties of the second shell are dictated by those of the first layer. The outer shell is apparently designed to stabilize/protect the inner-shell and complement/enhance its properties.

Negative electrospray ionization mass spectrometry: a method for sequencing and determining linkage position in oligosaccharides from branched hemicelluloses.

PubMed

Quéméner, Bernard; Vigouroux, Jacqueline; Rathahao, Estelle; Tabet, Jean Claude; Dimitrijevic, Aleksandra; Lahaye, Marc

2015-01-01

Xyloglucans of apple, tomato, bilberry and tamarind were hydrolyzed by commercial endo β-1-4-D-endoglucanase. The xylo-gluco-oligosaccharides (XylGos) released were separated on CarboPac PA 200 column in less than 15 min, and, after purification, they were structurally characterized by negative electrospray ionization mass spectrometry using a quadrupole time-of-flight (ESI-Q-TOF), a hybrid linear ion trap (LTQ)/Orbitrap and a hybrid quadrupole Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. In order to corroborate the fragmentation routes observed on XylGos, some commercial galacto-manno-oligosaccharides (GalMOs) and glucurono-xylo-oligosaccharides were also studied. The fragmentation pathways of the ionized GalMos were similar to those of XylGos ones. The product ion spectra were mainly characterized by prominent double cleavage (D) ions corresponding to the entire inner side chains. The directed fragmentation from the reducing end to the other end was observed for the main glycosylated backbone but also for the side-chains, allowing their complete sequencing. Relevant cross-ring cleavage ions from (0,2)X(j)-type revealed to be diagnostic of the 1-2-linked- glycosyl units from XylGos together with the 1-2-linked glucuronic acid unit from glucuronoxylans. Resonant activation in the LTQ Orbitrap allowed not only determining the type of all linkages but also the O-acetyl group location on fucosylated side-chains. Moreover, the fragmentation of the different side chains using the MS(n) capabilities of the LTQ/Orbitrap analyzer also allowed differentiating terminal arabinosyl and xylosyl substituents inside S and U side-chains of XylGos, respectively. The CID spectra obtained were very informative for distinction of isomeric structures differing only in their substitution pattern. These features together makes the fragmentation in negative ionization mode a relevant and powerful technique useful to highlight the subtle structural changes generally observed during the development of plant organs such as during fruit ripening and for the screening of cell wall mutants with altered hemicellulose structure. Copyright © 2015 John Wiley & Sons, Ltd.

Laser amplifier chain

DOEpatents

Hackel, R.P.

1992-10-20

A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain. 6 figs.

Comparison of the nutrient content of children's menu items at US restaurant chains, 2010-2014.

PubMed

Deierlein, Andrea L; Peat, Kay; Claudio, Luz

2015-08-15

To determine changes in the nutritional content of children's menu items at U.S. restaurant chains between 2010 and 2014. The sample consisted of 13 sit down and 16 fast-food restaurant chains ranked within the top 50 US chains in 2009. Nutritional information was accessed in June-July 2010 and 2014. Descriptive statistics were calculated for nutrient content of main dishes and side dishes, as well as for those items that were added, removed, or unchanged during the study period. Nutrient content of main dishes did not change significantly between 2010 and 2014. Approximately one-third of main dishes at fast-food restaurant chains and half of main dishes at sit down restaurant chains exceeded the 2010 Dietary Guidelines for Americans recommended levels for sodium, fat, and saturated fat in 2014. Improvements in nutrient content were observed for side dishes. At sit down restaurant chains, added side dishes contained over 50% less calories, fat, saturated fat, and sodium, and were more likely to contain fruits/vegetables compared to removed sides (p < 0.05 for all comparisons). Added side dishes at fast-food restaurant chains contained less saturated fat (p < 0.05). The majority of menu items, especially main dishes, available to children still contain high amounts of calories, fat, saturated fat, and sodium. Efforts must be made by the restaurant industry and policy makers to improve the nutritional content of children's menu items at restaurant chains to align with the Dietary Guidelines for Americans. Additional efforts are necessary to help parents and children make informed choices when ordering at restaurant chains.

In Vitro Enzymatic Synthesis of New Penicillins Containing Keto Acids as Side Chains

PubMed Central

Ferrero, Miguel A.; Reglero, Angel; Martínez-Blanco, Honorina; Fernández-Valverde, Martiniano; Luengo, Jose M.

1991-01-01

Seven different penicillins containing α-ketobutyric, β-ketobutyric, γ-ketovaleric, α-ketohexanoic, δ-ketohexanoic, ε-ketoheptanoic, and α-ketooctanoic acids as side chains have been synthesized in vitro by incubating the enzymes phenylacetyl coenzyme A (CoA) ligase from Pseudomonas putida and acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum with CoA, ATP, Mg2+, dithiothreitol, 6-aminopenicillanic acid, and the corresponding side chain precursor. PMID:1952871

Decomposition of total solvation energy into core, side-chains and water contributions: Role of cross correlations and protein conformational fluctuations in dynamics of hydration layer

NASA Astrophysics Data System (ADS)

Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

2017-09-01

Dynamical coupling between water and amino acid side-chain residues in solvation dynamics is investigated by selecting residues often used as natural probes, namely tryptophan, tyrosine and histidine, located at different positions on protein surface. Such differently placed residues are found to exhibit different timescales of relaxation. The total solvation response measured by the probe is decomposed in terms of its interactions with (i) protein core, (ii) side-chain and (iii) water. Significant anti cross-correlation among these contributions are observed. When the motion of the protein side-chains is quenched, solvation either becomes faster or slower depending on the location of the probe.

Improved packing of protein side chains with parallel ant colonies

PubMed Central

2014-01-01

Introduction The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. Methods We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. Results We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. Conclusions This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms. PMID:25474164

Uncovering the determinants of a highly perturbed tyrosine pKa in the active site of ketosteroid isomerase.

PubMed

Schwans, Jason P; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-11-05

Within the idiosyncratic enzyme active-site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near charged groups or within hydrophobic pockets, Tyr57 of a Pseudomonas putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semisynthesis, (13)C NMR spectroscopy, absorbance spectroscopy, and X-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from the introduction of nearby anionic groups, arises from accompanying active-site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen-bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen-bond donors, two Tyr side chains, and a water molecule positioned by other side chains and by a water-mediated hydrogen-bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active-site energetics. The extensive data set provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects.

Uncovering the Determinants of a Highly Perturbed Tyrosine pKa in the Active Site of Ketosteroid Isomerase†

PubMed Central

Schwans, Jason P.; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-01-01

Within the idiosyncratic enzyme active site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near to charged groups or within hydrophobic pockets, Tyr57 of a P. putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semi-synthesis, 13C NMR spectroscopy, absorbance spectroscopy, and x-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from introduction of nearby anionic groups arise from accompanying active site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen bond donors, two Tyr side chains and a water molecule, positioned by other side chains and by a water-mediated hydrogen bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions, rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active site energetics. The extensive dataset provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects. PMID:24151972

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

PubMed Central

2015-01-01

Summary Amino acids, whether natural, semisynthetic or synthetic, are among the most important and useful chiral building blocks available for organic chemical synthesis. In principle, they can function as inexpensive, chiral and densely functionalized starting materials. On the other hand, the use of amino acid starting materials routinely necessitates protective group chemistry, and in reality, large-scale preparations of even the simplest side-chain derivatives of many amino acids often become annoyingly strenuous due to the necessity of employing protecting groups, on one or more of the amino acid functionalities, during the synthetic sequence. However, in the case of hydroxyamino acids such as hydroxyproline, serine, threonine, tyrosine and 3,4-dihydroxyphenylalanine (DOPA), many O-acyl side-chain derivatives are directly accessible via a particularly expedient and scalable method not commonly applied until recently. Direct acylation of unprotected hydroxyamino acids with acyl halides or carboxylic anhydrides under appropriately acidic reaction conditions renders possible chemoselective O-acylation, furnishing the corresponding side-chain esters directly, on multigram-scale, in a single step, and without chromatographic purification. Assuming a certain degree of stability under acidic reaction conditions, the method is also applicable for a number of related compounds, such as various amino alcohols and the thiol-functional amino acid cysteine. While the basic methodology underlying this approach has been known for decades, it has evolved through recent developments connected to amino acid-derived chiral organocatalysts to become a more widely recognized procedure for large-scale preparation of many useful side-chain derivatives of hydroxyamino acids and related compounds. Such derivatives are useful in peptide chemistry and drug development, as amino acid amphiphiles for asymmetric catalysis, and as amino acid acrylic precursors for preparation of catalytically active macromolecular networks in the form of soluble polymers, crosslinked polymer beads or nanoparticulate systems. The objective of the present review is to increase awareness of the existence and convenience of this methodology, assess its competitiveness compared to newer and more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development. PMID:25977719

A novel branched side-chain-type sulfonated polyimide membrane with flexible sulfoalkyl pendants and trifluoromethyl groups for vanadium redox flow batteries

NASA Astrophysics Data System (ADS)

Li, Jinchao; Liu, Suqin; He, Zhen; Zhou, Zhi

2017-04-01

A novel branched side-chain-type sulfonated polyimide (6F-s-bSPI) membrane with accessible branching agents of melamine, hydrophobic trifluoromethyl groups (sbnd CF3), and flexible sulfoalkyl pendants is prepared by a high-temperature polycondensation and post-sulfonation method for use in vanadium redox flow batteries (VRFBs). The chemical structure of the 6F-s-bSPI membrane is confirmed by ATR-FTIR and 1H NMR spectra. The physico-chemical properties of the as-prepared 6F-s-bSPI membrane are systematically investigated and found to be strongly related to the specially designed structure. The 6F-s-bSPI membrane offers a reduced cost and possesses a significantly lowered vanadium ion permeability (1.18 × 10-7 cm2 min-1) compared to the linear SPI (2.25 × 10-7 cm2 min-1) and commercial Nafion 115 (1.36 × 10-6 cm2 min-1) membranes, prolonging the self-discharge duration of the VRFBs. In addition, the VRFB assembled with a 6F-s-bSPI membrane shows higher coulombic (98.3%-99.7%) and energy efficiencies (88.4%-66.12%) than that with a SPI or Nafion 115 membrane under current densities ranging from 20 to 100 mA cm-2. Moreover, the VRFB with a 6F-s-bSPI membrane delivers a stable cycling performance over 100 cycles with no decline in coulombic and energy efficiencies. These results show that the branched side-chain-type structure is a promising design to prepare excellent proton conductive membranes.

Theoretical calculation of pKa reveals an important role of Arg205 in the activity and stability of Streptomyces sp. N174 chitosanase.

PubMed

Fukamizo, T; Juffer, A H; Vogel, H J; Honda, Y; Tremblay, H; Boucher, I; Neugebauer, W A; Brzezinski, R

2000-08-18

Based on the crystal structure of chitosanase from Streptomyces sp. N174, we have calculated theoretical pK(a) values of the ionizable groups of this protein using a combination of the boundary element method and continuum electrostatics. The pK(a) value obtained for Arg(205), which is located in the catalytic cleft, was abnormally high (>20.0), indicating that the guanidyl group may interact strongly with nearby charges. Chitosanases possessing mutations in this position (R205A, R205H, and R205Y), produced by Streptomyces lividans expression system, were found to have less than 0.3% of the activity of the wild type enzyme and to possess thermal stabilities 4-5 kcal/mol lower than that of the wild type protein. In the crystal structure, the Arg(205) side chain is in close proximity to the Asp(145) side chain (theoretical pK(a), -1.6), which is in turn close to the Arg(190) side chain (theoretical pK(a), 17.7). These theoretical pK(a) values are abnormal, suggesting that both of these residues may participate in the Arg(205) interaction network. Activity and stability experiments using Asp(145)- and Arg(190)-mutated chitosanases (D145A and R190A) provide experimental data supporting the hypothesis derived from the theoretical pK(a) data and prompt the conclusion that Arg(205) forms a strong interaction network with Asp(145) and Arg(190) that stabilizes the catalytic cleft.

Factors governing the substitution of La3+ for Ca2+ and Mg2+ in metalloproteins: a DFT/CDM study.

PubMed

Dudev, Todor; Chang, Li-Ying; Lim, Carmay

2005-03-23

Trivalent lanthanide cations are extensively being used in biochemical experiments to probe various dication-binding sites in proteins; however, the factors governing the binding specificity of lanthanide cations for these binding sites remain unclear. Hence, we have performed systematic studies to evaluate the interactions between La3+ and model Ca2+ - and Mg2+ -binding sites using density functional theory combined with continuum dielectric methods. The calculations reveal the key factors and corresponding physical bases favoring the substitution of trivalent lanthanides for divalent Ca2+ and Mg2+ in holoproteins. Replacing Ca2+ or Mg2+ with La3+ is facilitated by (1) minimizing the solvent exposure and the flexibility of the metal-binding cavity, (2) freeing both carboxylate oxygen atoms of Asp/Glu side chains in the metal-binding site so that they could bind bidentately to La3+, (3) maximizing the number of metal-bound carboxylate groups in buried sites, but minimizing the number of metal-bound carboxylate groups in solvent-exposed sites, and (4) including an Asn/Gln side chain for sites lined with four Asp/Glu side chains. In proteins bound to both Mg2+ and Ca2+, La3+ would prefer to replace Ca2+, as compared to Mg2+. A second Mg2+-binding site with a net positive charge would hamper the Mg2+ --> La3+ exchange, as compared to the respective mononuclear site, although the La3+ substitution of the first native metal is more favorable than the second one. The findings of this work are in accord with available experimental data.

Chemical Modifications that Affect Nutritional and Functional Properties of Proteins.

ERIC Educational Resources Information Center

Richardson, T.; Kester, J. J.

1984-01-01

Discusses chemical alterations of selected amino acids resulting from environmental effects (photooxidations, pH extremes, thermally induced effects). Also dicusses use of intentional chemical derivatizations of various functional groups in amino acid residue side chains and how recombinant DNA techniques might be useful in structure/function…

Side-Chain Effects on the Thermoelectric Properties of Fluorene-Based Copolymers.

PubMed

Liang, Ansheng; Zhou, Xiaoyan; Zhou, Wenqiao; Wan, Tao; Wang, Luhai; Pan, Chengjun; Wang, Lei

2017-09-01

Three conjugated polymers with alkyl chains of different lengths are designed and synthesized, and their structure-property relationship as organic thermoelectric materials is systematically elucidated. All three polymers show similar photophysical properties, thermal properties, and mechanical properties; however, their thermoelectric performance is influenced by the length of their side chains. The length of the alkyl chain significantly influences the electrical conductivity of the conjugated polymers, and polymers with a short alkyl chain exhibit better conductivity than those with a long alkyl chain. The length of the alkyl chain has little effect on the Seebeck coefficient. Only a slight increase in the Seebeck coefficient is observed with the increasing length of the alkyl chain. The purpose of this study is to provide comprehensive insight into fine-tuning the thermoelectric properties of conjugated polymers as a function of side-chain engineering, thereby providing a novel perspective into the design of high-performance thermoelectric conjugated polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced production of longer side-chain polyhydroxyalkanoic acid with omega-aromatic group substitution in phaZ-disrupted Pseudomonas fluorescens BM07 mutant through unrelated carbon source cometabolism and salicylic acid beta-oxidation inhibition.

PubMed

Choi, Mun Hwan; Xu, Ju; Rho, Jong Kook; Zhao, Xu Ping; Yoon, Sung Chul

2010-06-01

The deletion of the intracellular polyhydroxyalkanoate (PHA) depolymerase gene (phaZ) in Pseudomonas fluorescens BM07 was found to increase more efficiently the levels of longer medium-chain-length (MCL) omega-aromatic monomer-units than in the wild-type strain when the cells were grown with a mixture of fructose and MCL omega-aromatic fatty acid in the presence of salicylic acid that is known as a beta-oxidation inhibitor in BM07 strain. When 11-phenoxyundecanoic acid was used as co-carbon source, the longest monomer-unit 3-hydroxy-11-phenoxyundecanoate, not reported in literature yet, was incorporated into the polymer chain up to approximately 10 mol%. An advantage of salicylic acid inhibition technique is that salicylic acid is not metabolized in BM07 strain, thus, the effective concentration of the inhibitor remaining constant throughout the cultivation. In conclusion, this new technique could be exploited for the enhanced production of side-chain modulated functional MCL-PHA with improved physicochemical properties in P. fluorescens BM07. (c) 2010 Elsevier Ltd. All rights reserved.

The position 68(E11) side chain in myoglobin regulates ligand capture, bond formation with heme iron, and internal movement into the xenon cavities.

PubMed

Dantsker, David; Roche, Camille; Samuni, Uri; Blouin, George; Olson, John S; Friedman, Joel M

2005-11-18

After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 --> 65 degrees C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B --> A, C --> A, and D --> A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B --> A and C --> A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.

A Strategy Combining Higher Energy C-Trap Dissociation with Neutral Loss- and Product Ion-Based MSn Acquisition for Global Profiling and Structure Annotation of Fatty Acids Conjugates

NASA Astrophysics Data System (ADS)

Bi, Qi-rui; Hou, Jin-jun; Yang, Min; Shen, Yao; Qi, Peng; Feng, Rui-hong; Dai, Zhuo; Yan, Bing-peng; Wang, Jian-wei; Shi, Xiao-jian; Wu, Wan-ying; Guo, De-an

2017-03-01

Fatty acids conjugates (FACs) are ubiquitous but found in trace amounts in the natural world. They are composed of multiple unknown substructures and side chains. Thus, FACs are difficult to be analyzed by traditional mass spectrometric methods. In this study, an integrated strategy was developed to global profiling and targeted structure annotation of FACs in complex matrix by LTQ Orbitrap. Dicarboxylic acid conjugated bufotoxins (DACBs) in Venenum bufonis (VB) were used as model compounds. The new strategy (abbreviated as HPNA) combined higher-energy C-trap dissociation (HCD) with product ion- (PI), neutral loss- (NL) based MSn (n ≥ 3) acquisition in both positive-ion mode and negative-ion mode. Several advantages are presented. First, various side chains were found under HCD in negative-ion mode, which included both known and unknown side chains. Second, DACBs with multiple side chains were simultaneously detected in one run. Compared with traditional quadrupole-based mass method, it greatly increased analysis throughput. Third, the fragment ions of side chain and steroids substructure could be obtained by PI- and NL-based MSn acquisition, respectively, which greatly increased the accuracy of the structure annotation of DACBs. In all, 78 DACBs have been discovered, of which 68 were new compounds; 25 types of substructure formulas and seven dicarboxylic acid side chains were found, especially five new side chains, including two saturated dicarboxylic acids [(azelaic acid (C9) and sebacic acid (C10)] and three unsaturated dicarboxylic acids (u-C8, u-C9, and u-C10). All these results greatly enriched the structures of DACBs in VB.

Galactose-depleted xyloglucan is dysfunctional and leads to dwarfism in Arabidopsis.

PubMed

Kong, Yingzhen; Peña, Maria J; Renna, Luciana; Avci, Utku; Pattathil, Sivakumar; Tuomivaara, Sami T; Li, Xuemei; Reiter, Wolf-Dieter; Brandizzi, Federica; Hahn, Michael G; Darvill, Alan G; York, William S; O'Neill, Malcolm A

2015-04-01

Xyloglucan is a polysaccharide that has important roles in the formation and function of the walls that surround growing land plant cells. Many of these plants synthesize xyloglucan that contains galactose in two different side chains (L and F), which exist in distinct molecular environments. However, little is known about the contribution of these side chains to xyloglucan function. Here, we show that Arabidopsis (Arabidopsis thaliana) mutants devoid of the F side chain galactosyltransferase MURUS3 (MUR3) form xyloglucan that lacks F side chains and contains much less galactosylated xylose than its wild-type counterpart. The galactose-depleted xyloglucan is dysfunctional, as it leads to mutants that are dwarfed with curled rosette leaves, short petioles, and short inflorescence stems. Moreover, cell wall matrix polysaccharides, including xyloglucan and pectin, are not properly secreted and instead accumulate within intracellular aggregates. Near-normal growth is restored by generating mur3 mutants that produce no detectable amounts of xyloglucan. Thus, cellular processes are affected more by the presence of the dysfunctional xyloglucan than by eliminating xyloglucan altogether. To identify structural features responsible for xyloglucan dysfunction, xyloglucan structure was modified in situ by generating mur3 mutants that lack specific xyloglucan xylosyltransferases (XXTs) or that overexpress the XYLOGLUCAN L-SIDE CHAIN GALACTOSYLTRANSFERASE2 (XLT2) gene. Normal growth was restored in the mur3-3 mutant overexpressing XLT2 and in mur3-3 xxt double mutants when the dysfunctional xyloglucan was modified by doubling the amounts of galactosylated side chains. Our study assigns a role for galactosylation in normal xyloglucan function and demonstrates that altering xyloglucan side chain structure disturbs diverse cellular and physiological processes. © 2015 American Society of Plant Biologists. All Rights Reserved.

Simple physics-based analytical formulas for the potentials of mean force of the interaction of amino-acid side chains in water. V. Like-charged side chains.

PubMed

Makowski, Mariusz; Liwo, Adam; Sobolewski, Emil; Scheraga, Harold A

2011-05-19

A new model of side-chain-side-chain interactions for charged side-chains of amino acids, to be used in the UNRES force-field, has been developed, in which a side chain consists of a nonpolar and a charged site. The interaction energy between the nonpolar sites is composed of a Gay-Berne and a cavity term; the interaction energy between the charged sites consists of a Lennard-Jones term, a Coulombic term, a generalized-Born term, and a cavity term, while the interaction energy between the nonpolar and charged sites is composed of a Gay-Berne and a polarization term. We parametrized the energy function for the models of all six pairs of natural like-charged amino-acid side chains, namely propionate-propionate (for the aspartic acid-aspartic acid pair), butyrate-butyrate (for the glutamic acid-glutamic acid pair), propionate-butyrate (for the aspartic acid-glutamic acid pair), pentylamine cation-pentylamine cation (for the lysine-lysine pair), 1-butylguanidine cation-1-butylguanidine cation (for the arginine-arginine pair), and pentylamine cation-1-butylguanidine cation (for the lysine-arginine pair). By using umbrella-sampling molecular dynamics simulations in explicit TIP3P water, we determined the potentials of mean force of the above-mentioned pairs as functions of distance and orientation and fitted analytical expressions to them. The positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the orientation of the molecules were well represented by analytical expressions for all systems. The values of the parameters of all the energy components are physically reasonable, which justifies use of such potentials in coarse-grain protein-folding simulations. © 2011 American Chemical Society

Functional modulation of a protein folding landscape via side-chain distortion

PubMed Central

Kelch, Brian A.; Salimi, Neema L.; Agard, David A.

2012-01-01

Ultrahigh-resolution (< 1.0 Å) structures have revealed unprecedented and unexpected details of molecular geometry, such as the deformation of aromatic rings from planarity. However, the functional utility of such energetically costly strain is unknown. The 0.83 Å structure of α-lytic protease (αLP) indicated that residues surrounding a conserved Phe side-chain dictate a rotamer which results in a ∼6° distortion along the side-chain, estimated to cost 4 kcal/mol. By contrast, in the closely related protease Streptomyces griseus Protease B (SGPB), the equivalent Phe adopts a different rotamer and is undistorted. Here, we report that the αLP Phe side-chain distortion is both functional and conserved in proteases with large pro regions. Sequence analysis of the αLP serine protease family reveals a bifurcation separating those sequences expected to induce distortion and those that would not, which correlates with the extent of kinetic stability. Structural and folding kinetics analyses of family members suggest that distortion of this side-chain plays a role in increasing kinetic stability within the αLP family members that use a large Pro region. Additionally, structural and kinetic folding studies of mutants demonstrate that strain alters the folding free energy landscape by destabilizing the transition state (TS) relative to the native state (N). Although side-chain distortion comes at a cost of foldability, it suppresses the rate of unfolding, thereby enhancing kinetic stability and increasing protein longevity under harsh extracellular conditions. This ability of a structural distortion to enhance function is unlikely to be unique to αLP family members and may be relevant in other proteins exhibiting side-chain distortions. PMID:22635267

Liquid Crystalline Polymers Containing Heterocycloalkane Mesogens. 1. Side-Chain Liquid Crystalline Polymethacrylates and Polycrylates Containing 2,5-Disubstituted-1,3-Dioxane Mesogens.

DTIC Science & Technology

1986-10-01

Report No. 2 Liquid Crystalline Polymers Containing Heterocycloalkane Mesogeus 1. Side-Chain Liquid Crystalline Polymethacrylates and . Polyacrylates...8217. " "-"-"-" " "" ’CS" i Liquid Crystalline Polymers Containing Heterocycloalkane Mesogens 1. Side-Chain Liquid Crystalline Polymethacrylates and Polyacrylates...University Cleveland, OH 44106 ABSTRACT Polymethacrylates and polyacrylates containing 2-(p-hydroxyphenyl)-5-(p-meth- oxyphenyl)-1,3-dioxane as a

Synthesis and solution self-assembly of side-chain cobaltocenium-containing block copolymers.

PubMed

Ren, Lixia; Hardy, Christopher G; Tang, Chuanbing

2010-07-07

The synthesis of side-chain cobaltocenium-containing block copolymers and their self-assembly in solution was studied. Highly pure monocarboxycobaltocenium was prepared and subsequently attached to side chains of poly(tert-butyl acrylate)-block-poly(2-hydroxyethyl acrylate), yielding poly(tert-butyl acrylate)-block-poly(2-acryloyloxyethyl cobaltoceniumcarboxylate). The cobaltocenium block copolymers exhibited vesicle morphology in the mixture of acetone and water, while micelles of nanotubes were formed in the mixture of acetone and chloroform.

How accurately do force fields represent protein side chain ensembles?

PubMed

Petrović, Dušan; Wang, Xue; Strodel, Birgit

2018-05-23

Although the protein backbone is the most fundamental part of the structure, the fine-tuning of side-chain conformations is important for protein function, for example, in protein-protein and protein-ligand interactions, and also in enzyme catalysis. While several benchmarks testing the performance of protein force fields for side chain properties have already been published, they often considered only a few force fields and were not tested against the same experimental observables; hence, they are not directly comparable. In this work, we explore the ability of twelve force fields, which are different flavors of AMBER, CHARMM, OPLS, or GROMOS, to reproduce average rotamer angles and rotamer populations obtained from extensive NMR studies of the 3 J and residual dipolar coupling constants for two small proteins: ubiquitin and GB3. Based on a total of 196 μs sampling time, our results reveal that all force fields identify the correct side chain angles, while the AMBER and CHARMM force fields clearly outperform the OPLS and GROMOS force fields in estimating rotamer populations. The three best force fields for representing the protein side chain dynamics are AMBER 14SB, AMBER 99SB*-ILDN, and CHARMM36. Furthermore, we observe that the side chain ensembles of buried amino acid residues are generally more accurately represented than those of the surface exposed residues. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

21. VIEW LOOKING FORWARD INTO STARBOARD SIDE OF CHAIN LOCKER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. VIEW LOOKING FORWARD INTO STARBOARD SIDE OF CHAIN LOCKER FROM CHAIN LOCKER BULKHEAD; PAWL BITT SHOWN IN EXTREME LEFT FOREGROUND, WITH APRON IN BACKGROUND. BREASTHOOK, SHELF AND CLAMP SHOWN AT TOP OF IMAGE - Pilot Schooner "Alabama", Moored in harbor at Vineyard Haven, Vineyard Haven, Dukes County, MA

Protonation-modulated localization of excess electrons in histidine aqueous solutions revealed by ab initio molecular dynamics simulations: anion-centered versus cation-centered localization.

PubMed

Gao, Liang; Bu, Yuxiang

2017-05-31

In this work, we present an ab initio molecular dynamics simulation study on the interaction of an excess electron (EE) with histidine in its aqueous solution. Two different configurations of histidine (imidazole group protonated or not) are considered to reflect its different existing forms in neutral or slightly acidic surroundings. The simulation results indicate that localizations of EEs in different aqueous histidine solutions are quite different and are strongly affected by protonation of the side chain imidazole group and are thus pH-controlled. In neutral aqueous histidine solution, an EE localizes onto the carboxyl anionic group of the amino acid backbone after a relatively lengthy diffuse state, performing just like in an aliphatic amino acid solution. But in weakly acidic solution in which the side chain imidazole group is protonated, an EE undergoes a short lifetime diffuse state and finally localizes on the protonated imidazole group. We carefully examine these two different localization dynamics processes and analyze the competition between different dominating groups in their corresponding electron localization mechanisms. To explain the difference, we investigate the frontier molecular orbitals of these two systems and find that their energy levels and compositions are important to determine these differences. These findings can provide helpful information to understand the interaction mechanisms of low energy EEs with amino acids and even oligopeptides, especially with aromatic rings.

Characterization of Leachianone G 2″ -Dimethylallyltransferase, a Novel Prenyl Side-Chain Elongation Enzyme for the Formation of the Lavandulyl Group of Sophoraflavanone G in Sophora flavescens Ait. Cell Suspension Cultures

PubMed Central

Zhao, Ping; Inoue, Kenichiro; Kouno, Isao; Yamamoto, Hirobumi

2003-01-01

Leachianone G (LG) 2′′-dimethylallyltransferase, a novel prenyl side-chain elongation enzyme, was identified in Sophora flavescens Ait. cultured cells. The enzyme transfers a dimethylallyl group to the 2′′ position of another dimethylallyl group attached at position 8 of LG to form sophoraflavanone G, a branched monoterpenoid-conjugated flavanone characteristic to this plant. This membrane-bound dimethylallyltransferase required Mg2+ (optimum concentration was 10 mm) for the reaction and had an optimum pH of 8.8. It utilized dimethylallyl diphosphate as the sole prenyl donor, and the 2′-hydroxy function in LG was indispensable to the activity. The apparent Km values for dimethylallyl diphosphate and LG were 59 and 2.3 μm, respectively. Subcellular localization of three enzymes that participated in the formation of the lavandulyl group was also investigated by sucrose density gradient centrifugation. Two prenyltransferases, naringenin 8-dimethylallyltransferase and LG 2′′-dimethylallyltransferase, were localized in the plastids, whereas 8-dimethylallylnaringenin 2′-hydroxylase, which catalyzes the crucial step in the lavandulyl-group formation, was associated with the endoplasmic reticulum. These results suggest the close cooperation between the plastids and the endoplasmic reticulum in the formation of lavandulyl groups. PMID:14551337

Chemical construction and structural permutation of neurotoxic natural product, antillatoxin: importance of the three-dimensional structure of the bulky side chain

PubMed Central

INOUE, Masayuki

2014-01-01

Antillatoxin 1 is a unique natural product that displays potent neurotoxic and neuritogenic activities through activation of voltage-gated sodium channels. The peptidic macrocycle of 1 was attached to a side chain with an exceptionally high degree of methylation. In this review, we discuss the total synthesis and biological evaluation of 1 and its analogues. First we describe an efficient synthetic route to 1. This strategy enabled the unified preparation of nine side chain analogues. Structure-activity relationship studies of these analogues revealed that subtle side chain modification leads to dramatic changes in activity, and detailed structural analyses indicated the importance of the overall size and three dimensional shape of the side chain. Based on these data, we designed and synthesized a photoresponsive analogue, proving that the activity of 1 was modulated via a photochemical reaction. The knowledge accumulated through these studies will be useful for the rational design of new tailor-made molecules to control the function and behavior of ion channels. PMID:24522155

Effect of Non-fullerene Acceptors' Side Chains on the Morphology and Photovoltaic Performance of Organic Solar Cells.

PubMed

Zhang, Cai'e; Feng, Shiyu; Liu, Yahui; Hou, Ran; Zhang, Zhe; Xu, Xinjun; Wu, Youzhi; Bo, Zhishan

2017-10-04

Three indacenodithieno[3,2-b]thiophene (IT) cored small molecular acceptors (ITIC-SC6, ITIC-SC8, and ITIC-SC2C6) were synthesized, and the influence of side chains on their performances in solar cells was systematically probed. Our investigations have demonstrated the variation of side chains greatly affects the charge dissociation, charge mobility, and morphology of the donor:acceptor blend films. ITIC-SC2C6 with four branched side chains showed improved solubility, which can ensure the polymer donor to form favorable fibrous nanostructure during the drying of the blend film. Consequently, devices based on PBDB-ST:ITIC-SC2C6 demonstrated higher charge mobility, more effective exciton dissociation, and the optimal power conversion efficiency up to 9.16% with an FF of 0.63, a J sc of 15.81 mA cm -2 , and a V oc of 0.92 V. These results reveal that the side chain engineering is a valid way of tuning the morphology of blend films and further improving PCE in polymer solar cells.

Epitope mapping of imidazolium cations in ionic liquid-protein interactions unveils the balance between hydrophobicity and electrostatics towards protein destabilisation.

PubMed

Silva, Micael; Figueiredo, Angelo Miguel; Cabrita, Eurico J

2014-11-14

We investigated imidazolium-based ionic liquid (IL) interactions with human serum albumin (HSA) to discern the level of cation interactions towards protein stability. STD-NMR spectroscopy was used to observe the imidazolium IL protons involved in direct binding and to identify the interactions responsible for changes in Tm as accessed by differential scanning calorimetry (DSC). Cations influence protein stability less than anions but still significantly. It was found that longer alkyl side chains of imidazolium-based ILs (more hydrophobic) are associated with a higher destabilisation effect on HSA than short-alkyl groups (less hydrophobic). The reason for such destabilisation lies on the increased surface contact area of the cation with the protein, particularly on the hydrophobic contacts promoted by the terminus of the alkyl chain. The relevance of the hydrophobic contacts is clearly demonstrated by the introduction of a polar moiety in the alkyl chain: a methoxy or alcohol group. Such structural modification reduces the degree of hydrophobic contacts with HSA explaining the lesser extent of protein destabilisation when compared to longer alkyl side chain groups: above [C2mim](+). Competition STD-NMR experiments using [C2mim](+), [C4mim](+) and [C2OHmim](+) also validate the importance of the hydrophobic interactions. The combined effect of cation and anion interactions was explored using (35)Cl NMR. Such experiments show that the nature of the cation has no influence on the anion-protein contacts, still the nature of the anion modulates the cation-protein interaction. Herein we propose that more destabilising anions are likely to be a result of a partial contribution from the cation as a direct consequence of the different levels of interaction (cation-anion pair and cation-protein).

From Chemistry to Behavior. Molecular Structure and Bioactivity of Repellents against Ixodes ricinus Ticks

PubMed Central

Fabbro, Simone Del; Nazzi, Francesco

2013-01-01

Tick-borne zoonoses are considered as emerging diseases. Tick repellents represent an effective tool for reducing the risk of tick bite and pathogens transmission. Previous work demonstrated the repellent activity of the phenylpropanoid eugenol against Ixodes ricinus; here we investigate the relationship between molecular structure and repellency in a group of substances related to that compound. We report the biological activity of 18 compounds varying for the presence/number of several moieties, including hydroxyl and methoxy groups and carbon side-chain. Each compound was tested at different doses with a bioassay designed to measure repellency against individual tick nymphs. Both vapor pressure and chemical features of the tested compounds appeared to be related to repellency. In particular, the hydroxyl and methoxy groups as well as the side-chain on the benzene ring seem to play a role. These results are discussed in light of available data on chemical perception in ticks. In the course of the study new repellent compounds were identified; the biological activity of some of them (at least as effective as the “gold standard” repellent DEET) appears to be very promising from a practical point of view. PMID:23805329

Simulated infrared spectra of triflic acid during proton dissociation.

PubMed

Laflamme, Patrick; Beaudoin, Alexandre; Chapaton, Thomas; Spino, Claude; Soldera, Armand

2012-05-05

Vibrational analysis of triflic acid (TfOH) at different water uptakes was conducted. This molecule mimics the sulfonate end of the Nafion side-chain. As the proton leaves the sulfonic acid group, structural changes within the Nafion side-chain take place. They are revealed by signal shifts in the infrared spectrum. Molecular modeling is used to follow structural modifications that occur during proton dissociation. To confirm the accuracy of the proposed structures, infrared spectra were computed via quantum chemical modeling based on density functional theory. The requirement to use additional diffuse functions in the basis set is discussed. Comparison between simulated infrared spectra of 1 and 2 acid molecules with different water contents and experimental data was performed. An accurate description of infrared spectra for systems containing 2 TfOH was obtained. Copyright © 2012 Wiley Periodicals, Inc.

Effect of vitamin A deprivation on the cholesterol side-chain cleavage enzyme activity of testes and ovaries of rats (Short Communication)

PubMed Central

Jayaram, M.; Murthy, S. K.; Ganguly, J.

1973-01-01

The cholesterol side-chain cleavage enzyme activity is decreased considerably at the mild stage of vitamin A deficiency in rat testes and ovaries and the decrease in activity becomes more pronounced with progress of deficiency. Supplementation of the deficient rats with retinyl acetate, but not retinoic acid, restores the enzyme activity to normal values. The cholesterol side-chain cleavage enzyme of adrenals is not affected by any of the above treatments. PMID:4772624

Formation and stability of water-soluble, molecular polyelectrolyte complexes: effects of charge density, mixing ratio, and polyelectrolyte concentration.

PubMed

Shovsky, Alexander; Varga, Imre; Makuska, Ricardas; Claesson, Per M

2009-06-02

The formation of complexes with stoichiometric (1:1) as well as nonstoichiometric (2:1) and (1:2) compositions between oppositely charged synthetic polyelectrolytes carrying strong ionic groups and significantly different molecular weights is reported in this contribution. Poly(sodium styrenesulfonate) (NaPSS) was used as polyanion, and a range of copolymers with various molar ratios of the poly(methacryloxyethyltrimethylammonium) chloride, poly(METAC), and the nonionic poly(ethylene oxide) ether methacrylate, poly(PEO45MEMA), were used as polycations. Formation and stability of PECs have been investigated by dynamic and static light scattering (LS), turbidity, and electrophoretic mobility measurements as a function of polyelectrolyte solution concentration, charge density of the cationic polyelectrolyte, and mixing ratio. The data obtained demonstrate that in the absence of PEO45 side chains the 100% charged polymer (polyMETAC) formed insoluble PECs with PSS that precipitate from solution when exact stoichiometry is achieved. In nonstoichiometric complexes (1:2) and (2:1) large colloidally stable aggregates were formed. The presence of even a relatively small amount of PEO45 side chains (25%) in the cationic copolymer was sufficient for preventing precipitation of the formed stoichiometric and nonstoichiometric complexes. These PEC's are sterically stabilized by the PEO45 chains. By further increasing the PEO45 side-chain content (50 and 75%) of the cationic copolymer, small, water-soluble molecular complexes could be formed. The data suggest that PSS molecules and the charged backbone of the cationic brush form a compact core, and with sufficiently high PEO45 chain density (above 25%) molecular complexes are formed that are stable over prolonged times.

The role of amino acid side chains in stabilizing dipeptides: the laser ablation Fourier transform microwave spectrum of Ac-Val-NH2.

PubMed

León, I; Alonso, E R; Mata, S; Cabezas, C; Rodríguez, M A; Grabow, J-U; Alonso, J L

2017-09-20

The steric effects imposed by the isopropyl group of valine in the conformational stabilization of the capped dipeptide N-acetyl-l-valinamide (Ac-Val-NH 2 ) have been studied by laser ablation molecular beam Fourier transform microwave (LA-MB-FTMW) spectroscopy. The rotational and quadrupole coupling constants of the two 14 N nuclei determined in this work show that this dipeptide exists as a mixture of C 7 and C 5 conformers in the supersonic expansion. The conformers are stabilized by a C[double bond, length as m-dash]OH-N intramolecular hydrogen bond closing a seven- or a five-membered ring, respectively. The observation of both conformers is in good agreement with previous results on the related dipeptides containing different residues, confirming that the polarity/non-polarity of the side chains of the amino acid is responsible for the conformational locking/unlocking. The voluminous isopropyl group is not able to prevent the less stable C 5 conformer from forming but it destabilizes the C[double bond, length as m-dash]OH-N interaction.

Poly(Amido Amine)s Containing Agmatine and Butanol Side Chains as Efficient Gene Carriers.

PubMed

Won, Young-Wook; Ankoné, Marc; Engbersen, Johan F J; Feijen, Jan; Kim, Sung Wan

2016-04-01

A new type of bioreducible poly(amido amine) copolymer is synthesized by the Michael addition polymerization of cystamine bisacrylamide (CBA) with 4-aminobutylguanidine (agmatine, AGM) and 4-aminobutanol (ABOL). Since the positively charged guanidinium groups of AGM and the hydroxybutyl groups of ABOL in the side chains have shown to improve the overall transfection efficiency of poly(amido amine)s, it is hypothesized that poly(CBA-ABOL/AGM) synthesized at the optimal ratio of both components would result in high transfection efficiency and minimal toxicity. In this study, a series of the poly(CBA-ABOL/AGM) copolymers is synthesized as gene carriers. The polymers are characterized and luciferase transfection efficiencies of the polymers in various cell lines are investigated to select the ideal ratio between AGM and ABOL. The poly(CBA-ABOL/AGM) containing 80% AGM and 20% ABOL has shown the best transfection efficiency with the lowest cytotoxicity, indicating that this polymer is very promising as a potent and nontoxic gene carrier. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Directed evolution of a model primordial enzyme provides insights into the development of the genetic code.

PubMed

Müller, Manuel M; Allison, Jane R; Hongdilokkul, Narupat; Gaillon, Laurent; Kast, Peter; van Gunsteren, Wilfred F; Marlière, Philippe; Hilvert, Donald

2013-01-01

The contemporary proteinogenic repertoire contains 20 amino acids with diverse functional groups and side chain geometries. Primordial proteins, in contrast, were presumably constructed from a subset of these building blocks. Subsequent expansion of the proteinogenic alphabet would have enhanced their capabilities, fostering the metabolic prowess and organismal fitness of early living systems. While the addition of amino acids bearing innovative functional groups directly enhances the chemical repertoire of proteomes, the inclusion of chemically redundant monomers is difficult to rationalize. Here, we studied how a simplified chorismate mutase evolves upon expanding its amino acid alphabet from nine to potentially 20 letters. Continuous evolution provided an enhanced enzyme variant that has only two point mutations, both of which extend the alphabet and jointly improve protein stability by >4 kcal/mol and catalytic activity tenfold. The same, seemingly innocuous substitutions (Ile→Thr, Leu→Val) occurred in several independent evolutionary trajectories. The increase in fitness they confer indicates that building blocks with very similar side chain structures are highly beneficial for fine-tuning protein structure and function.

The serotype-specific glucose side chain of rhamnose-glucose polysaccharides is essential for adsorption of bacteriophage M102 to Streptococcus mutans.

PubMed

Shibata, Yukie; Yamashita, Yoshihisa; van der Ploeg, Jan R

2009-05-01

Bacteriophage M102 is a virulent siphophage that propagates in some serotype c Streptococcus mutans strains, but not in S. mutans of serotype e, f or k. The serotype of S. mutans is determined by the glucose side chain of rhamnose-glucose polysaccharide (RGP). Because the first step in the bacteriophage infection process is adsorption of the phage, it was investigated whether the serotype specificity of phage M102 was determined by adsorption. M102 adsorbed to all tested serotype c strains, but not to strains of different serotypes. Streptococcus mutans serotype c mutants defective in the synthesis of the glucose side chain of RGP failed to adsorb phage M102. These results suggest that the glucose side chain of RGP acts as a receptor for phage M102.

Exploring the impact of the side-chain length on peptide/RNA binding events.

PubMed

Sbicca, Lola; González, Alejandro López; Gresika, Alexandra; Di Giorgio, Audrey; Closa, Jordi Teixido; Tejedor, Roger Estrada; Andréola, Marie-Line; Azoulay, Stéphane; Patino, Nadia

2017-07-19

The impact of the amino-acid side-chain length on peptide-RNA binding events has been investigated using HIV-1 Tat derived peptides as ligands and the HIV-1 TAR RNA element as an RNA model. Our studies demonstrate that increasing the length of all peptide side-chains improves unexpectedly the binding affinity (K D ) but reduces the degree of compactness of the peptide-RNA complex. Overall, the side-chain length appears to modulate in an unpredictable way the ability of the peptide to compete with the cognate TAR RNA partner. Beyond the establishment of non-intuitive fundamental relationships, our results open up new perspectives in the design of effective RNA ligand competitors, since a large number of them have already been identified but few studies report on the modulation of the biological activity by modifying in the same way the length of all chains connecting RNA recognition motives to the central scaffold of a ligand.

Side-chain hydroxylation in the metabolism of 8-aminoquinoline antiparasitic agents.

PubMed

Idowu, O R; Peggins, J O; Brewer, T G

1995-01-01

Primaquine, 8-(4-amino-1-methylbutylamino)-6-methoxyquinoline, is an antimalarial 8-aminoquinoline derivative. Although it has been in use since 1952, its metabolism has not been clearly defined. This is due to the instability of the expected aminophenol metabolites and their amphoteric nature, which makes their isolation difficult. Recent studies on the metabolism of WR 238605, a new primaquine analog, has shown that these problems may be solved by extracting the metabolites in the presence of ethyl chloroformate. Subsequent identification of the ethoxycarbonyl derivatives of the metabolites has made it possible to define the in vitro metabolism of primaquine. The primary metabolic pathways of primaquine involved hydroxylation of the phenyl ring of the quinoline nucleus and C-hydroxylation of the 3'-position of the 8-aminoalkylamino side chain. Ring-hydroxylation of primaquine gives rise to 5-hydroxyprimaquine, which on demethylation produces 5-hydroxy-6-demethylprimaquine. Side-chain hydroxylation of primaquine gives rise to 3'-hydroxyprimaquine, which also undergoes O-demethylation to 3'-hydroxy-6-demethylprimaquine. 6-Demethylprimaquine, a putative metabolite of primaquine, also underwent metabolism involving 3'-hydroxylation of the side chain. WR 6026, 8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline, is an antileishmanial 8-aminoquinoline derivative. The in vitro metabolism of WR 6026 also results in the formation of side chain-oxygenated metabolites. The present results, together with previous observations on the metabolism of WR 238605 and closely related primaquine analog, suggest that side-chain oxygenation is an important metabolic pathway of antiparasitic 8-aminoquinoline compounds in general.

Conformational exchange of aromatic side chains characterized by L-optimized TROSY-selected ¹³C CPMG relaxation dispersion.

PubMed

Weininger, Ulrich; Respondek, Michal; Akke, Mikael

2012-09-01

Protein dynamics on the millisecond time scale commonly reflect conformational transitions between distinct functional states. NMR relaxation dispersion experiments have provided important insights into biologically relevant dynamics with site-specific resolution, primarily targeting the protein backbone and methyl-bearing side chains. Aromatic side chains represent attractive probes of protein dynamics because they are over-represented in protein binding interfaces, play critical roles in enzyme catalysis, and form an important part of the core. Here we introduce a method to characterize millisecond conformational exchange of aromatic side chains in selectively (13)C labeled proteins by means of longitudinal- and transverse-relaxation optimized CPMG relaxation dispersion. By monitoring (13)C relaxation in a spin-state selective manner, significant sensitivity enhancement can be achieved in terms of both signal intensity and the relative exchange contribution to transverse relaxation. Further signal enhancement results from optimizing the longitudinal relaxation recovery of the covalently attached (1)H spins. We validated the L-TROSY-CPMG experiment by measuring fast folding-unfolding kinetics of the small protein CspB under native conditions. The determined unfolding rate matches perfectly with previous results from stopped-flow kinetics. The CPMG-derived chemical shift differences between the folded and unfolded states are in excellent agreement with those obtained by urea-dependent chemical shift analysis. The present method enables characterization of conformational exchange involving aromatic side chains and should serve as a valuable complement to methods developed for other types of protein side chains.

Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

PubMed

Gauthier, Marc A; Klok, Harm-Anton

2008-06-21

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

CADB: Conformation Angles DataBase of proteins

PubMed Central

Sheik, S. S.; Ananthalakshmi, P.; Bhargavi, G. Ramya; Sekar, K.

2003-01-01

Conformation Angles DataBase (CADB) provides an online resource to access data on conformation angles (both main-chain and side-chain) of protein structures in two data sets corresponding to 25% and 90% sequence identity between any two proteins, available in the Protein Data Bank. In addition, the database contains the necessary crystallographic parameters. The package has several flexible options and display facilities to visualize the main-chain and side-chain conformation angles for a particular amino acid residue. The package can also be used to study the interrelationship between the main-chain and side-chain conformation angles. A web based JAVA graphics interface has been deployed to display the user interested information on the client machine. The database is being updated at regular intervals and can be accessed over the World Wide Web interface at the following URL: http://144.16.71.148/cadb/. PMID:12520049

Molecular Packing of High-Mobility Diketo Pyrrolo-Pyrrole Polymer Semiconductors with Branched Alkyl Side Chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

X Zhang; L Richter; D DeLongchamp

We describe a series of highly soluble diketo pyrrolo-pyrrole (DPP)-bithiophene copolymers exhibiting field effect hole mobilities up to 0.74 cm{sup 2} V{sup -1} s{sup -1}, with a common synthetic motif of bulky 2-octyldodecyl side groups on the conjugated backbone. Spectroscopy, diffraction, and microscopy measurements reveal a transition in molecular packing behavior from a preferentially edge-on orientation of the conjugated plane to a preferentially face-on orientation as the attachment density of the side chains increases. Thermal annealing generally reduces both the face-on population and the misoriented edge-on domains. The highest hole mobilities of this series were obtained from edge-on molecular packingmore » and in-plane liquid-crystalline texture, but films with a bimodal orientation distribution and no discernible in-plane texture exhibited surprisingly comparable mobilities. The high hole mobility may therefore arise from the molecular packing feature common to the entire polymer series: backbones that are strictly oriented parallel to the substrate plane and coplanar with other backbones in the same layer.« less

Collision-Induced Dissociation of Deprotonated Peptides. Relative Abundance of Side-Chain Neutral Losses, Residue-Specific Product Ions, and Comparison with Protonated Peptides

NASA Astrophysics Data System (ADS)

Liang, Yuxue; Neta, Pedatsur; Yang, Xiaoyu; Stein, Stephen E.

2018-03-01

High-accuracy MS/MS spectra of deprotonated ions of 390 dipeptides and 137 peptides with three to six residues are studied. Many amino acid residues undergo neutral losses from their side chains. The most abundant is the loss of acetaldehyde from threonine. The abundance of losses from the side chains of other amino acids is estimated relative to that of threonine. While some amino acids lose the whole side chain, others lose only part of it, and some exhibit two or more different losses. Side-chain neutral losses are less abundant in the spectra of protonated peptides, being significant mainly for methionine and arginine. In addition to the neutral losses, many amino acid residues in deprotonated peptides produce specific negative ions after peptide bond cleavage. An expanded list of fragment ions from protonated peptides is also presented and compared with those of deprotonated peptides. Fragment ions are mostly different for these two cases. These lists of fragments are used to annotate peptide mass spectral libraries and to aid in the confirmation of specific amino acids in peptides. [Figure not available: see fulltext.

Collision-Induced Dissociation of Deprotonated Peptides. Relative Abundance of Side-Chain Neutral Losses, Residue-Specific Product Ions, and Comparison with Protonated Peptides.

PubMed

Liang, Yuxue; Neta, Pedatsur; Yang, Xiaoyu; Stein, Stephen E

2018-03-01

High-accuracy MS/MS spectra of deprotonated ions of 390 dipeptides and 137 peptides with three to six residues are studied. Many amino acid residues undergo neutral losses from their side chains. The most abundant is the loss of acetaldehyde from threonine. The abundance of losses from the side chains of other amino acids is estimated relative to that of threonine. While some amino acids lose the whole side chain, others lose only part of it, and some exhibit two or more different losses. Side-chain neutral losses are less abundant in the spectra of protonated peptides, being significant mainly for methionine and arginine. In addition to the neutral losses, many amino acid residues in deprotonated peptides produce specific negative ions after peptide bond cleavage. An expanded list of fragment ions from protonated peptides is also presented and compared with those of deprotonated peptides. Fragment ions are mostly different for these two cases. These lists of fragments are used to annotate peptide mass spectral libraries and to aid in the confirmation of specific amino acids in peptides. Graphical Abstract ᅟ.

Positioning of the carboxamide side chain in 11-oxo-11H-indeno[1,2-b]quinolinecarboxamide anticancer agents: effects on cytotoxicity.

PubMed

Deady, L W; Desneves, J; Kaye, A J; Finlay, G J; Baguley, B C; Denny, W A

2001-02-01

A series of 11-oxo-11H-indeno[1,2-b]quinolines bearing a carboxamide-linked cationic side chain at various positions on the chromophore was studied to determine structure-activity relationships between cytotoxicity and the position of the side chain. The compounds were prepared by Pfitzinger synthesis from an appropriate isatin and 1-indanone, followed by various oxidative steps, to generate the required carboxylic acids. The 4- and 6-carboxamides (with the side chain on a terminal ring, off the short axis of the chromophore) were effective cytotoxins. The dimeric 4- and 6-linked analogues were considerably more cytotoxic than the parent monomers, but had broadly similar activities. In contrast, analogues with side chains at the 8-position (on a terminal ring but off the long axis of the chromophore) or 10-position (off the short axis of the chromophore but in a central ring) were drastically less effective. The 4,10- and 6,10-biscarboxamides had activities between those of the corresponding parent monocarboxamides. The first of these showed good activity against advanced subcutaneous colon 38 tumours in mice.

Tension amplification in tethered layers of bottle-brush polymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leuty, Gary M.; Tsige, Mesfin; Grest, Gary S.

2016-02-26

In this paper, molecular dynamics simulations of a coarse-grained bead–spring model have been used to study the effects of molecular crowding on the accumulation of tension in the backbone of bottle-brush polymers tethered to a flat substrate. The number of bottle-brushes per unit surface area, Σ, as well as the lengths of the bottle-brush backbones N bb (50 ≤ N bb ≤ 200) and side chains N sc (50 ≤ N sc ≤ 200) were varied to determine how the dimensions and degree of crowding of bottle-brushes give rise to bond tension amplification along the backbone, especially near the substrate.more » From these simulations, we have identified three separate regimes of tension. For low Σ, the tension is due solely to intramolecular interactions and is dominated by the side chain repulsion that governs the lateral brush dimensions. With increasing Σ, the interactions between bottle-brush polymers induce compression of the side chains, transmitting increasing tension to the backbone. For large Σ, intermolecular side chain repulsion increases, forcing side chain extension and reorientation in the direction normal to the surface and transmitting considerable tension to the backbone.« less

Gingerol-derivatives: emerging new therapy against human drug-resistant MCF-7.

PubMed

Ibrahim, Ahmed S; Sobh, Mohamed A M; Eid, Hossam Mohammed; Salem, Amgad; Elbelasi, Hossam Hamza; El-Naggar, Mai H; AbdelBar, Fatma M; Sheashaa, Hussein; Sobh, Mohamed A; Badria, Farid A

2014-10-01

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols' wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC50 = 30.4 μM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol's SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol's cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.

Characterization of cationic polymers by asymmetric flow field-flow fractionation and multi-angle light scattering-A comparison with traditional techniques.

PubMed

Wagner, Michael; Pietsch, Christian; Tauhardt, Lutz; Schallon, Anja; Schubert, Ulrich S

2014-01-17

In the field of nanomedicine, cationic polymers are the subject of intensive research and represent promising carriers for genetic material. The detailed characterization of these carriers is essential since the efficiency of gene delivery strongly depends on the properties of the used polymer. Common characterization methods such as size exclusion chromatography (SEC) or mass spectrometry (MS) suffer from problems, e.g. missing standards, or even failed for cationic polymers. As an alternative, asymmetrical flow field-flow fractionation (AF4) was investigated. Additionally, analytical ultracentrifugation (AUC) and (1)H NMR spectroscopy, as well-established techniques, were applied to evaluate the results obtained by AF4. In this study, different polymers of molar masses between 10 and 120kgmol(-1) with varying amine functionalities in the side chain or in the polymer backbone were investigated. To this end, some of the most successful gene delivery agents, namely linear poly(ethylene imine) (LPEI) (only secondary amines in the backbone), branched poly(ethylene imine) (B-PEI) (secondary and tertiary amino groups in the backbone, primary amine end groups), and poly(l-lysine) (amide backbone and primary amine side chains), were characterized. Moreover, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), poly(2-(amino)ethyl methacrylate) (PAEMA), and poly(2-(tert-butylamino)ethyl methacrylate) (PtBAEMA) as polymers with primary, secondary, and tertiary amines in the side chain, have been investigated. Reliable results were obtained for all investigated polymers by AF4. In addition, important factors for all methods were evaluated, e.g. the influence of different elution buffers and AF4 membranes. Besides this, the correct determination of the partial specific volume and the suppression of the polyelectrolyte effect are the most critical issues for AUC investigations. Copyright © 2013 Elsevier B.V. All rights reserved.

Critical role of alkyl chain branching of organic semiconductors in enabling solution-processed N-channel organic thin-film transistors with mobility of up to 3.50 cm² V(-1) s(-1).

PubMed

Zhang, Fengjiao; Hu, Yunbin; Schuettfort, Torben; Di, Chong-an; Gao, Xike; McNeill, Christopher R; Thomsen, Lars; Mannsfeld, Stefan C B; Yuan, Wei; Sirringhaus, Henning; Zhu, Daoben

2013-02-13

Substituted side chains are fundamental units in solution processable organic semiconductors in order to achieve a balance of close intermolecular stacking, high crystallinity, and good compatibility with different wet techniques. Based on four air-stable solution-processed naphthalene diimides fused with 2-(1,3-dithiol-2-ylidene)malononitrile groups (NDI-DTYM2) that bear branched alkyl chains with varied side-chain length and different branching position, we have carried out systematic studies on the relationship between film microstructure and charge transport in their organic thin-film transistors (OTFTs). In particular synchrotron measurements (grazing incidence X-ray diffraction and near-edge X-ray absorption fine structure) are combined with device optimization studies to probe the interplay between molecular structure, molecular packing, and OTFT mobility. It is found that the side-chain length has a moderate influence on thin-film microstructure but leads to only limited changes in OTFT performance. In contrast, the position of branching point results in subtle, yet critical changes in molecular packing and leads to dramatic differences in electron mobility ranging from ~0.001 to >3.0 cm(2) V(-1) s(-1). Incorporating a NDI-DTYM2 core with three-branched N-alkyl substituents of C(11,6) results in a dense in-plane molecular packing with an unit cell area of 127 Å(2), larger domain sizes of up to 1000 × 3000 nm(2), and an electron mobility of up to 3.50 cm(2) V(-1) s(-1), which is an unprecedented value for ambient stable n-channel solution-processed OTFTs reported to date. These results demonstrate that variation of the alkyl chain branching point is a powerful strategy for tuning of molecular packing to enable high charge transport mobilities.

Structure and function studies on enzymes with a catalytic carboxyl group(s): from ribonuclease T1 to carboxyl peptidases

PubMed Central

TAKAHASHI, Kenji

2013-01-01

A group of enzymes, mostly hydrolases or certain transferases, utilize one or a few side-chain carboxyl groups of Asp and/or Glu as part of the catalytic machinery at their active sites. This review follows mainly the trail of studies performed by the author and his colleagues on the structure and function of such enzymes, starting from ribonuclease T1, then extending to three major types of carboxyl peptidases including aspartic peptidases, glutamic peptidases and serine-carboxyl peptidases. PMID:23759941

A Study on the Impact of Poly(3-hexylthiophene) Chain Length and Other Applied Side-Chains on the NO2 Sensing Properties of Conducting Graft Copolymers

PubMed Central

Kepska, Kinga

2018-01-01

The detection and concentration measurements of low concentrations of nitrogen dioxide (NO2) are important because of its negative effects on human health and its application in many fields of industry and safety systems. In our approach, conducting graft copolymers based on the poly(3-hexylthiophene) (P3HT) conducting polymer and other side-chains, polyethylene glycol (PEG) and dodec-1-en, grafted on a poly(methylhydrosiloxane) backbone, were investigated. The grafts containing PEG (PEGSil) and dodec-1-en (DodecSil) in two variants, namely, fractions with shorter (hexane fraction -H) and longer (chloroform fraction -CH) side-chains of P3HT, were tested as receptor structures in NO2 gas sensors. Their responses to NO2, within the concentration range of 1–20 ppm, were investigated in an nitrogen atmosphere at different operating temperatures—room temperature (RT) = 25 °C, 50 °C, and 100 °C. The results indicated that both of the copolymers with PEG side-chains had higher responses to NO2 than the materials with dodec-1-en side-chains. Furthermore, the results indicated that, in both cases, H fractions were more sensitive than CH fractions. The highest response to 1 ppm of NO2, from the investigated graft copolymers, had PEGSil H, which indicated a response of 1330% at RT and 1980% at 100 °C. The calculated lower-limit of the detection of this material is lower than 300 ppb of NO2 at 100 °C. This research indicated that graft copolymers of P3HT had great potential for low temperature NO2 sensing, and that the proper choice of other side-chains in graft copolymers can improve their gas sensing properties. PMID:29558448

Biologically produced acid precipitable polymeric lignin

DOEpatents

Crawford, Don L.; Pometto, III, Anthony L.

1984-01-01

A water soluble, acid precipitable polymeric degraded lignin (APPL), having a molecular weight of at least 12,000 daltons, and comprising, by percentage of total weight, at least three times the number of phenolic hydroxyl groups and carboxylic acid groups present in native lignin. The APPL may be modified by chemical oxidation and reduction to increase its phenolic hydroxyl content and reduce the number of its antioxidant inhibitory side chains, thereby improving antioxidant properties.

Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain.

PubMed

Iwaniuk, Daniel P; Whetmore, Eric D; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C; Roepe, Paul D; Wolf, Christian

2009-09-15

We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain.

Characterization of the Deoxyguanosine–Lysine Cross-Link of Methylglyoxal

PubMed Central

2015-01-01

Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA–protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side chains. However, the chemical nature of the methylglyoxal induced DPC have not been determined. We have examined the reaction of methylglyoxal, deoxyguanosine (dGuo), and Nα-acetyllysine (AcLys) and determined the structure of the cross-link to be the N2-ethyl-1-carboxamide with the lysine side chain amino group (1). The cross-link was identified by mass spectrometry and the structure confirmed by comparison to a synthetic sample. Further, the cross-link between methylglyoxal, dGuo, and a peptide (AcAVAGKAGAR) was also characterized. The mechanism of cross-link formation is likely to involve an Amadori rearrangement. PMID:24801980

Poly-dimethylsiloxane derivates side chains effect on syntan functionalized Polyamide fabric

NASA Astrophysics Data System (ADS)

Migani, V.; Weiss, H.; Massafra, M. R.; Merlo, A.; Colleoni, C.; Rosace, G.

2011-02-01

Poly-dimethylsiloxane (PDMS) polymers finishing of Polyamide-6,6 (PA66) fabrics involves ionic interactions between reactive groups on the PDMS polymers and the ones of the textile fabric. Such interactions could be strengthened by a pretreatment with a fixing agent to promote either ion-ion and H-bonding and ion-dipole forces. These forces could contribute towards the building of substantial PDMS-PA66 systems and the achieving of better adhesion properties to fabrics. Four different silicone polymers based on PDMS were applied on a synthetic tanning agent (syntan) finished Polyamide-6,6 fabric under acid conditions. Soxhlet extraction method and ATR FT-IR technique were used to investigate the application conditions. The finishing parameters such as pH and temperature together with fastness, mechanical and performance properties of the treated samples were studied and related to PDMS side chains effect on syntan functionalized Polyamide fabric.

Surface Propensity of Atmospherically Relevant Amino Acids Studied by XPS.

PubMed

Mocellin, Alexandra; Gomes, Anderson Herbert de Abreu; Araújo, Oscar Cardoso; de Brito, Arnaldo Naves; Björneholm, Olle

2017-04-27

Amino acids constitute an important fraction of the water-soluble organic nitrogen (WSON) compounds in aerosols and are involved in many processes in the atmosphere. In this work, we applied X-ray photoelectron spectroscopy (XPS) to study aqueous solutions of four amino acids, glycine, alanine, valine, and methionine, in their zwitterionic forms. We found that amino acids with hydrophilic side chains and smaller size, GLY and ALA, tend to stay in the bulk of the liquid, while the hydrophobic and bigger amino acids, VAL and MET, are found to concentrate more on the surface. We found experimental evidence that the amino acids have preferential orientation relative to the surface, with the hydrophobic side chain being closer to the surface than the hydrophilic carboxylate group. The observed amino acid surface propensity has implications in atmospheric science as the surface interactions play a central role in cloud droplet formation, and they should be considered in climate models.

Phase Transition in Biopolymer Hydrogels Based on Glycine (g), Valine (v), Proline (p), and Isoleucine (i)

NASA Astrophysics Data System (ADS)

Lee, Jonghwi; Urry, Dan W.; Macosko, Christopher W.

2000-03-01

Selectively modified elastic protein-based polymers demonstrate diverse energy conversions by means of the control of a phase transition resulting from the sensitivity to stimuli of the hydrophobic association. Among these polymers, poly(GVGVP), poly(GVGIP) and analogues of poly(GVGVP) containing carboxylic acid or amino functional groups as side chains were cross-linked and their swelling behavior was studied. Regardless of cross-linking method, reversible phase transitions can be observed in the swelling of all cross-linked polymers by changing temperature and pH, where relevant. Decreased cross-link density leads to increased swelling ratio as the transition becomes more pronounced. Fibers, chemically cross-linked after formation, exhibit anisotropic dimensional changes on changing the temperature. Gamma-irradiation cross-linked poly(GVGVP) exhibited a more distinct phase transition than modified poly(GVGVP) with ion pairs between side chains, which were partially converted to amide cross-links.

Probing Charge Transport through Peptide Bonds.

PubMed

Brisendine, Joseph M; Refaely-Abramson, Sivan; Liu, Zhen-Fei; Cui, Jing; Ng, Fay; Neaton, Jeffrey B; Koder, Ronald L; Venkataraman, Latha

2018-02-15

We measure the conductance of unmodified peptides at the single-molecule level using the scanning tunneling microscope-based break-junction method, utilizing the N-terminal amine group and the C-terminal carboxyl group as gold metal-binding linkers. Our conductance measurements of oligoglycine and oligoalanine backbones do not rely on peptide side-chain linkers. We compare our results with alkanes terminated asymmetrically with an amine group on one end and a carboxyl group on the other to show that peptide bonds decrease the conductance of an otherwise saturated carbon chain. Using a newly developed first-principles approach, we attribute the decrease in conductance to charge localization at the peptide bond, which reduces the energy of the frontier orbitals relative to the Fermi energy and the electronic coupling to the leads, lowering the tunneling probability. Crucially, this manifests as an increase in conductance decay of peptide backbones with increasing length when compared with alkanes.

Fragmentation of alpha-Radical Cations of Arginine-Containing Peptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laskin, Julia; Yang, Zhibo; Ng, Dominic C.

2010-04-01

Fragmentation pathways of peptide radical cations, M+, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of CoIII(salen)-peptide complexes [salen = N,N´-ethylenebis (salicylideneaminato)]. Subsequent hydrogen abstraction from the -carbon of the side chain followed by Ca-C bond cleavage results in the loss of a neutral side chain and formation of an a-radical cation with the radical site localized on the a-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of a-radicals when the basic arginine side chain wasmore » present in the sequence. In contrast, proton-driven fragmentation dominates CID spectra of a-radicals produced via the loss of the arginine side chain. Our results suggest that in most cases radical migration precedes fragmentation of large peptide radical cations.« less

Self-Assembly of Narrowly Dispersed Brush Diblock Copolymers with Domain Spacing more than 100 nm

NASA Astrophysics Data System (ADS)

Gu, Weiyin; Sveinbjornsson, Benjamin; Hong, Sung Woo; Grubbs, Robert; Russell, Thomas

2012-02-01

Self-assembled structures of high molecular weight (MW), narrow molecular weight distribution brush block copolymers containing polylactic acid (PLA) and polystyrene (PS) side chains with similar MWs were studied in both the melt and thin films. The polynorbornene-backbone-based brush diblock copolymers containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing over 100 nm, as revealed by SAXS, GISAXS and AFM. The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state. The length of side chains also played a significant role in terms of controlling the domain size. As the degree of polymerization (DP) increased, the symmetric brush diblock copolymers with longer side chains tended to form larger lamellar microdomains in comparison to those that have the same DP but shorter side chains.

Microscopic insights into the NMR relaxation based protein conformational entropy meter

PubMed Central

Kasinath, Vignesh; Sharp, Kim A.; Wand, A. Joshua

2013-01-01

Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven pro! teins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side-chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion - the NMR-derived generalized order parameters - as a proxy from which to derive changes in protein conformational entropy. PMID:24007504

Stabilization Effect of Amino Acid Side Chains in Peptide Assemblies on Graphite Studied by Scanning Tunneling Microscopy.

PubMed

Guo, Yuanyuan; Hou, Jingfei; Zhang, Xuemei; Yang, Yanlian; Wang, Chen

2017-04-19

An analysis is presented of the effects of amino acid side chains on peptide assemblies in ambient conditions on a graphite surface. The molecularly resolved assemblies of binary peptides are examined with scanning tunneling microscopy. A comparative analysis of the assembly structures reveals that the lamellae width has an appreciable dependence on the peptide sequence, which could be considered as a manifestation of a stabilizing effect of side-chain moieties of amino acids with high (phenylalanine) and low (alanine, asparagine, histidine and aspartic acid) propensities for aggregation. These amino acids are representative for the chemical structures involving the side chains of charged (histidine and aspartic acid), aromatic (phenylalanine), hydrophobic (alanine), and hydrophilic (asparagine) amino acids. These results might provide useful insight for understanding the effects of sequence on the assembly of surface-bound peptides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural, electronic, topological and vibrational properties of a series of N-benzylamides derived from Maca (Lepidium meyenii) combining spectroscopic studies with ONION calculations

NASA Astrophysics Data System (ADS)

Chain, Fernando E.; Ladetto, María Florencia; Grau, Alfredo; Catalán, César A. N.; Brandán, Silvia Antonia

2016-02-01

In the present work, the structural, topological and vibrational properties of four members of the N-benzylamides series derived from Maca (Lepidium meyenii) whose names are, N-benzylpentadecanamide, N-benzylhexadecanamide, N-benzylheptadecanamide and N-benzyloctadecanamide, were studied combining the FTIR, FT-Raman and 1H and 13C-NMR spectroscopies with density functional theory (DFT) and ONION calculations. Furthermore, the N-benzylacetamide, N-benzylpropilamide and N-benzyl hexanamide derivatives were also studied in order to compare their properties with those computed for the four macamides. These seven N-benzylamides series have a common structure, C8H8NO-R, being R the side chain [-(CH2)n-CH3] with a variable n number of CH2 groups. Here, the atomic charges, molecular electrostatic potentials, stabilization energies, topological properties of those macamides were analyzed as a function of the number of C atoms of the side chain while the frontier orbitals were used to compute the gap energies and some descriptors in order to predict their reactivities and behaviors in function of the longitude of the side chain. Here, the force fields, the complete vibrational assignments and the corresponding force constants were only reported for N-benzylacetamide, N-benzyl hexanamide and N-benzylpentadecanamide due to the high number of vibration normal modes that present the remains macamides.

Amide or Amine: Determining the Origin of the 3300 cm−1 NH Mode in Protein SFG Spectra Using 15N Isotope Labels

PubMed Central

Weidner, Tobias; Breen, Nicholas F.; Drobny, Gary P.; Castner, David G.

2009-01-01

Sum frequency generation (SFG) vibrational spectroscopy has been employed in biomaterials research and protein adsorption studies with growing success in recent years. A number of studies focusing on understanding SFG spectra of proteins and peptides at different interfaces have laid the foundation for future, more complex studies. In many cases a strong NH mode near 3300 cm−1 is observed in the SFG spectra, but the relationship of this mode to the peptide structure is uncertain since it has been assigned to either a backbone amide mode or a side chain related amine resonance. A thorough understanding of the SFG spectra of these first model systems is an important first step for future experiments. To clarify the origin of the NH SFG mode we studied 15N isotopically labeled 14-amino acid amphiphilic model peptides composed of lysine (K) and leucine (L) in an α-helical secondary structure (LKα14) that were adsorbed onto charged surfaces in situ at the solid-liquid interface. 15N substitution at the terminal amine group of the lysine side chains resulted in a red-shift of the NH mode of 9 cm−1 on SiO2 and 13 cm−1 on CaF2. This clearly shows the 3300 cm−1 NH feature is associated with side chain NH stretches and not with backbone amide modes. PMID:19873996

Amide or amine: determining the origin of the 3300 cm(-1) NH mode in protein SFG spectra using 15N isotope labels.

PubMed

Weidner, Tobias; Breen, Nicholas F; Drobny, Gary P; Castner, David G

2009-11-26

Sum frequency generation (SFG) vibrational spectroscopy has been employed in biomaterials research and protein adsorption studies with growing success in recent years. A number of studies focusing on understanding SFG spectra of proteins and peptides at different interfaces have laid the foundation for future, more complex studies. In many cases, a strong NH mode near 3300 cm(-1) is observed in the SFG spectra, but the relationship of this mode to the peptide structure is uncertain, since it has been assigned to either a backbone amide mode or a side chain related amine resonance. A thorough understanding of the SFG spectra of these first model systems is an important first step for future experiments. To clarify the origin of the NH SFG mode, we studied (15)N isotopically labeled 14-amino acid amphiphilic model peptides composed of lysine (K) and leucine (L) in an alpha-helical secondary structure (LKalpha14) that were adsorbed onto charged surfaces in situ at the solid-liquid interface. (15)N substitution at the terminal amine group of the lysine side chains resulted in a red-shift of the NH mode of 9 cm(-1) on SiO(2) and 13 cm(-1) on CaF(2). This clearly shows the 3300 cm(-1) NH feature is associated with side chain NH stretches and not with backbone amide modes.

Oxidative transformation of tunichromes - Model studies with 1,2-dehydro-N-acetyldopamine and N-acetylcysteine.

PubMed

Kuang, Qun F; Abebe, Adal; Evans, Jason; Sugumaran, Manickam

2017-08-01

Tunichromes are 1,2-dehydrodopa containing bioactive peptidyl derivatives found in blood cells of several tunicates. They have been implicated in metal sequestering, tunic formation, wound healing and defense reaction. Earlier studies conducted on these compounds indicate their extreme liability, high reactivity and easy oxidative polymerization. Their reactions are also complicated by the presence of multiple dehydrodopyl units. Since they have been invoked in crosslinking and covalent binding, to understand the reactivities of these novel compounds, we have taken a simple model compound that possess the tunichrome reactive group viz., 1,2-dehydro-N-acetyldopamine (Dehydro NADA) and examined its reaction with N-acetylcysteine in presence of oxygen under both enzymatic and nonenzymatic conditions. Ultraviolet and visible spectral studies of reaction mixtures containing dehydro NADA and N-acetylcysteine in different molar ratios indicated the production of side chain and ring adducts of N-acetylcysteine to dehydro NADA. Liquid chromatography and mass spectral studies supported this contention and confirmed the production of several different products. Mass spectral analysis of these products show the potentials of dehydro NADA to form side chain adducts that can lead to polymeric products. This is the first report demonstrating the ability of dehydro dopyl units to form adducts and crosslinks with amino acid side chains. Copyright © 2017 Elsevier Inc. All rights reserved.

Succinimide Formation from an NGR-Containing Cyclic Peptide: Computational Evidence for Catalytic Roles of Phosphate Buffer and the Arginine Side Chain.

PubMed

Kirikoshi, Ryota; Manabe, Noriyoshi; Takahashi, Ohgi

2017-02-16

The Asn-Gly-Arg (NGR) motif and its deamidation product iso Asp-Gly-Arg ( iso DGR) have recently attracted considerable attention as tumor-targeting ligands. Because an NGR-containing peptide and the corresponding iso DGR-containing peptide target different receptors, the spontaneous NGR deamidation can be used in dual targeting strategies. It is well known that the Asn deamidation proceeds via a succinimide derivative. In the present study, we computationally investigated the mechanism of succinimide formation from a cyclic peptide, c[CH₂CO-NGRC]-NH₂, which has recently been shown to undergo rapid deamidation in a phosphate buffer. An H₂PO₄ - ion was explicitly included in the calculations. We employed the density functional theory using the B3LYP functional. While geometry optimizations were performed in the gas phase, hydration Gibbs energies were calculated by the SM8 (solvation model 8) continuum model. We have found a pathway leading to the five-membered ring tetrahedral intermediate in which both the H₂PO₄ - ion and the Arg side chain act as catalyst. This intermediate, once protonated at the NH₂ group on the five-membered ring, was shown to easily undergo NH₃ elimination leading to the succinimide formation. This study is the first to propose a possible catalytic role for the Arg side chain in the NGR deamidation.

Caution is required in interpretation of mutations in the voltage sensing domain of voltage gated channels as evidence for gating mechanisms.

PubMed

Kariev, Alisher M; Green, Michael E

2015-01-12

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R → C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is -SH (reactive form -S-); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain -OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations.

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE PAGES

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; ...

2015-11-03

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics

NASA Astrophysics Data System (ADS)

Mansbach, Rachael A.; Ferguson, Andrew L.

2015-03-01

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics.

PubMed

Mansbach, Rachael A; Ferguson, Andrew L

2015-03-14

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Density Functional Study of Stacking Structures and Electronic Behaviors of AnE-PV Copolymer.

PubMed

Dong, Chuan-Ding; Beenken, Wichard J D

2016-10-10

In this work, we report an in-depth investigation on the π-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the π-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport.

Role of Tryptophan Side Chain Dynamics on the Trp-Cage Mini-Protein Folding Studied by Molecular Dynamics Simulations

PubMed Central

Kannan, Srinivasaraghavan; Zacharias, Martin

2014-01-01

The 20 residue Trp-cage mini-protein is one of smallest proteins that adopt a stable folded structure containing also well-defined secondary structure elements. The hydrophobic core is arranged around a single central Trp residue. Despite several experimental and simulation studies the detailed folding mechanism of the Trp-cage protein is still not completely understood. Starting from fully extended as well as from partially folded Trp-cage structures a series of molecular dynamics simulations in explicit solvent and using four different force fields was performed. All simulations resulted in rapid collapse of the protein to on average relatively compact states. The simulations indicate a significant dependence of the speed of folding to near-native states on the side chain rotamer state of the central Trp residue. Whereas the majority of intermediate start structures with the central Trp side chain in a near-native rotameric state folded successfully within less than 100 ns only a fraction of start structures reached near-native folded states with an initially non-native Trp side chain rotamer state. Weak restraining of the Trp side chain dihedral angles to the state in the folded protein resulted in significant acceleration of the folding both starting from fully extended or intermediate conformations. The results indicate that the side chain conformation of the central Trp residue can create a significant barrier for controlling transitions to a near native folded structure. Similar mechanisms might be of importance for the folding of other protein structures. PMID:24563686

Adapting Poisson-Boltzmann to the self-consistent mean field theory: Application to protein side-chain modeling

NASA Astrophysics Data System (ADS)

Koehl, Patrice; Orland, Henri; Delarue, Marc

2011-08-01

We present an extension of the self-consistent mean field theory for protein side-chain modeling in which solvation effects are included based on the Poisson-Boltzmann (PB) theory. In this approach, the protein is represented with multiple copies of its side chains. Each copy is assigned a weight that is refined iteratively based on the mean field energy generated by the rest of the protein, until self-consistency is reached. At each cycle, the variational free energy of the multi-copy system is computed; this free energy includes the internal energy of the protein that accounts for vdW and electrostatics interactions and a solvation free energy term that is computed using the PB equation. The method converges in only a few cycles and takes only minutes of central processing unit time on a commodity personal computer. The predicted conformation of each residue is then set to be its copy with the highest weight after convergence. We have tested this method on a database of hundred highly refined NMR structures to circumvent the problems of crystal packing inherent to x-ray structures. The use of the PB-derived solvation free energy significantly improves prediction accuracy for surface side chains. For example, the prediction accuracies for χ1 for surface cysteine, serine, and threonine residues improve from 68%, 35%, and 43% to 80%, 53%, and 57%, respectively. A comparison with other side-chain prediction algorithms demonstrates that our approach is consistently better in predicting the conformations of exposed side chains.

Microbial biodegradation of aromatic alkanoic naphthenic acids is affected by the degree of alkyl side chain branching

PubMed Central

Johnson, Richard J; Smith, Ben E; Sutton, Paul A; McGenity, Terry J; Rowland, Steven J; Whitby, Corinne

2011-01-01

Naphthenic acids (NAs) occur naturally in oil sands and enter the environment through natural and anthropogenic processes. NAs comprise toxic carboxylic acids that are difficult to degrade. Information on NA biodegradation mechanisms is limited, and there are no studies on alkyl branched aromatic alkanoic acid biodegradation, despite their contribution to NA toxicity and recalcitrance. Increased alkyl side chain branching has been proposed to explain NA recalcitrance. Using soil enrichments, we examined the biodegradation of four aromatic alkanoic acid isomers that differed in alkyl side chain branching: (4′-n-butylphenyl)-4-butanoic acid (n-BPBA, least branched); (4′-iso-butylphenyl)-4-butanoic acid (iso-BPBA); (4′-sec-butylphenyl)-4-butanoic acid (sec-BPBA) and (4′-tert-butylphenyl)-4-butanoic acid (tert-BPBA, most branched). n-BPBA was completely metabolized within 49 days. Mass spectral analysis confirmed that the more branched isomers iso-, sec- and tert-BPBA were transformed to their butylphenylethanoic acid (BPEA) counterparts at 14 days. The BPEA metabolites were generally less toxic than BPBAs as determined by Microtox assay. n-BPEA was further transformed to a diacid, showing that carboxylation of the alkyl side chain occurred. In each case, biodegradation of the carboxyl side chain proceeded through beta-oxidation, which depended on the degree of alkyl side chain branching, and a BPBA degradation pathway is proposed. Comparison of 16S rRNA gene sequences at days 0 and 49 showed an increase and high abundance at day 49 of Pseudomonas (sec-BPBA), Burkholderia (n-, iso-, tert-BPBA) and Sphingomonas (n-, sec-BPBA). PMID:20962873

Immobilization of paracetamol and benzocaine pro-drug derivatives as long-range self-organized monolayers on graphite.

PubMed

Popoff, Alexandre; Fichou, Denis

2008-05-01

We show here by means of scanning tunneling microscopy (STM) at the liquid/solid interface that paracetamol and benzocaine molecules bearing a long aliphatic chain can be immobilized on highly oriented pyrolitic graphite (HOPG) as perfectly ordered two-dimensional domains extending over several hundreds of nanometers. In both cases, high-resolution STM images reveal that compounds 1 and 2 self-assemble into parallel lamellae having a head-to-head arrangement. The paracetamol heads of 1 are in a zigzag position with entangled n-dodecyloxy side chains while benzocaine heads of compound 2 are perfectly aligned as a double row and have their palmitic side chains on either sides of the head alignment. We attribute the very long-range ordering of these two pro-drug derivatives on HOPG to the combined effects of intermolecular H-bonding on one side and Van der Waals interactions between aliphatic side chains and graphite on the other side. The 2D immobilization of pro-drug derivatives via a non-destructive physisorption mechanism could prove to be useful for applications such as drug delivery if it can be realized on a biocompatible substrate.

Catalytic carbene transfer allows the direct customization of cyclic purine dinucleotides.

PubMed

Fei, Na; Häussinger, Daniel; Blümli, Seraina; Laventie, Benoît-Joseph; Bizzini, Lorenzo D; Zimmermann, Kaspar; Jenal, Urs; Gillingham, Dennis

2014-08-11

We describe a simple method for the direct modification of nucleobases in cyclic purine dinucleotides, important signalling molecules in both prokaryotes and eukaryotes. The method tolerates all members of the cyclic dinucleotide family and could be used to modulate their function or introduce useful side-chains such as fluorophores and photo-crosslinking groups.

From labdanes to drimanes. Degradation of the side chain of dihydrozamoranic acid.

PubMed

Rodilla, Jesús M L; Díez, D; Urones, J G; Rocha, Pedro M

2004-04-30

A new route for the degradation of the saturated side chain of dihydrozamoranic acid has been devised, giving an advanced intermediate, compound 14, useful for the synthesis of insect antifeedants such as warburganal and polygodial.

Synthesis and serotonergic activity of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT(1B)-like receptor.

PubMed

Moloney, G P; Martin, G R; Mathews, N; Milne, A; Hobbs, H; Dodsworth, S; Sang, P Y; Knight, C; Williams, M; Maxwell, M; Glen, R C

1999-07-15

The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over alpha(1)-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of approximately 4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2, N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2, N-benzylcarboxamide group and its close proximity to the 3-side chain.

Scale-Dependent Stiffness and Internal Tension of a Model Brush Polymer

NASA Astrophysics Data System (ADS)

Berezney, John P.; Marciel, Amanda B.; Schroeder, Charles M.; Saleh, Omar A.

2017-09-01

Bottle-brush polymers exhibit closely grafted side chains that interact by steric repulsion, thereby causing stiffening of the main polymer chain. We use single-molecule elasticity measurements of model brush polymers to quantify this effect. We find that stiffening is only significant on long length scales, with the main chain retaining flexibility on short scales. From the elasticity data, we extract an estimate of the internal tension generated by side-chain repulsion; this estimate is consistent with the predictions of blob-based scaling theories.

The Inherent Conformational Preferences of Glutamine-Containing Peptides: the Role for Side-Chain Backbone Hydrogen Bonds

NASA Astrophysics Data System (ADS)

Walsh, Patrick S.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.

2015-06-01

Glutamine is widely known to be found in critical regions of peptides which readily fold into amyloid fibrils, the structures commonly associated with Alzheimer's disease and glutamine repeat diseases such as Huntington's disease. Building on previous single-conformation data on Gln-containing peptides containing an aromatic cap on the N-terminus (Z-Gln-OH and Z-Gln-NHMe), we present here single-conformation UV and IR spectra of Ac-Gln-NHBn and Ac-Ala-Gln-NHBn, with its C-terminal benzyl cap. These results point towards side-chain to backbone hydrogen bonds dominating the structures observed in the cold, isolated environment of a molecular beam. We have identified and assigned three main conformers for Ac-Gln-NHBn all involving primary side-chain to backbone interactions. Ac-Ala-Gln-NHBn extends the peptide chain by one amino acid, but affords an improvement in the conformational flexibility. Despite this increase in the flexibility, only a single conformation is observed in the gas-phase: a structure which makes use of both side-chain-to-backbone and backbone-to-backbone hydrogen bonds.

Influence of the strength of the smectic order on the backbone anisotropy of side-chain liquid crystal polymers as revealed by SANS

NASA Astrophysics Data System (ADS)

Noirez, L.; Keller, P.; Cotton, J. P.

1992-06-01

It is proposed that the strength of the smectic order determines the backbone anisotropy of side-chain liquid crystal polymers. Here this strength increases with the length of the alkyl terminal group of the mesogens. Two liquid crystal polymethacrylates differing only by the mesogenic tails —OCH3 and —OC4H9 are considered. The backbone anisotropy of these polymers is measured by small angle neutron scattering (SANS) whereas the smectic order is evaluated from the intensity of the 001 Bragg peak. Il est proposé que la qualité de l'ordre smectique détermine l'anisotropie du squelette de polymères mésomorphes en peigne confinés dans les lamelles. Ici l'ordre smectique est augmenté en allongeant le groupe alkyl terminal des mésogènes. Nous étudions deux polyméthacrylates cristal liquide qui ne différent que par leurs groupes terminaux : —OCH3 et —OC4H9. L'anisotropie du squellete est mesurée par diffusion de neutrons aux petits angles tandis que l'ordre smectique est évalué à l'aide de l'intensité du pic de Bragg 001.

A versatile platform for precise synthesis of asymmetric molecular brush in one shot.

PubMed

Xu, Binbin; Feng, Chun; Huang, Xiaoyu

2017-08-24

Asymmetric molecular brushes emerge as a unique class of nanostructured polymers, while their versatile synthesis keeps a challenge for chemists. Here we show the synthesis of well-defined asymmetric molecular double-brushes comprising two different side chains linked to the same repeat unit along the backbone by one-pot concurrent atom transfer radical polymerization (ATRP) and Cu-catalyzed azide/alkyne cycloaddition (CuAAC) reaction. The double-brushes are based on a poly(Br-acrylate-alkyne) homopolymer possessing an alkynyl for CuAAC reaction and a 2-bromopropionate initiating group for ATRP in each repeat unit. The versatility of this one-shot approach is demonstrated by CuAAC reaction of alkynyl/poly(ethylene oxide)-N 3 and ATRP of various monomers. We also show the quantitative conversion of pentafluorophenyl ester groups to amide groups in side chains, allowing for the further fabrication of diverse building blocks. This work provides a versatile platform for facile synthesis of Janus-type double-brushes with structural and functional control, in a minimum number of reactions.Producing well-defined polymer compositions and structures facilitates their use in many different applications. Here the authors show the synthesis of well-defined asymmetric double-brushes by a one-pot concurrent atom transfer radical polymerization and Cu-catalyzed Click reaction.

Interaction of anesthetic molecules with α-helix and polyproline II extended helix of long-chain poly-L-lysine

NASA Astrophysics Data System (ADS)

Cieślik-Boczula, Katarzyna; Rospenk, Maria

2018-01-01

The effect of halothane, enflurane, sevoflurane, and isoflurane molecules, as volatile anesthetics, on the α-helices and polyproline II extended helices (PPII) of long-chain poly-L-lysine (PLL) were studied using Fourier-transform infrared and vibrational circular dichroism spectroscopy. Uncharged and charged α-helices, as well as charged extended PPII helices, were subjected to anesthetic actions in solvents with different pD values or methanol to water ratios. A crucial factor responsible for hindering the anesthetic-PLL interactions is shown to be the ionization of amino groups of the PLL side chains. The α-helix to β-sheet transition was triggered only for the uncharged α-helical structures of PLL by the nonpolar anesthetics under study.

O-Acetyl Side-Chains in Monosaccharides: Redundant NMR Spin-Couplings and Statistical Models for Acetate Ester Conformational Analysis.

PubMed

Turney, Toby; Pan, Qingfeng; Sernau, Luke; Carmichael, Ian; Zhang, Wenhui; Wang, Xiaocong; Woods, Robert J; Serianni, Anthony S

2017-01-12

α- and β-d-glucopyranose monoacetates 1-3 were prepared with selective 13 C enrichment in the O-acetyl side-chain, and ensembles of 13 C- 1 H and 13 C- 13 C NMR spin-couplings (J-couplings) were measured involving the labeled carbons. Density functional theory (DFT) was applied to a set of model structures to determine which J-couplings are sensitive to rotation of the ester bond θ. Eight J-couplings ( 1 J CC , 2 J CH , 2 J CC , 3 J CH , and 3 J CC ) were found to be sensitive to θ, and four equations were parametrized to allow quantitative interpretations of experimental J-values. Inspection of J-coupling ensembles in 1-3 showed that O-acetyl side-chain conformation depends on molecular context, with flanking groups playing a dominant role in determining the properties of θ in solution. To quantify these effects, ensembles of J-couplings containing four values were used to determine the precision and accuracy of several 2-parameter statistical models of rotamer distributions across θ in 1-3. The statistical method used to generate these models has been encoded in a newly developed program, MA'AT, which is available for public use. These models were compared to O-acetyl side-chain behavior observed in a representative sample of crystal structures, and in molecular dynamics (MD) simulations of O-acetylated model structures. While the functional form of the model had little effect on the precision of the calculated mean of θ in 1-3, platykurtic models were found to give more precise estimates of the width of the distribution about the mean (expressed as circular standard deviations). Validation of these 2-parameter models to interpret ensembles of redundant J-couplings using the O-acetyl system as a test case enables future extension of the approach to other flexible elements in saccharides, such as glycosidic linkage conformation.

Vapor pressures of 1,3-dialkylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquids with long alkyl chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rocha, Marisa A. A., E-mail: lbsantos@fc.up.pt, E-mail: marisa.alexandra.rocha@gmail.com; Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven; Coutinho, João A. P.

2014-10-07

This work presents the vapor pressure at several temperatures for the 1,3-dialkylimidazolium bis(trifluoromethylsulfonyl)imide series, [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (N = 14, 16, 18, and 20), measured by a Knudsen effusion method combined with a quartz crystal microbalance. The thermodynamic properties of vaporization of the ionic liquids under study are analysed together with the results obtained previously for the shorter alkyl chain length [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (N = 2, 4, 6, 8, 10, and 12), in order to evaluate the effect of the alkyl side chains of the cation and to get additional insights concerning the nanostructuration of ionic liquids.more » The symmetry effect is explored, based on the comparison with the asymmetric imidazolium based ionic liquids, [C{sub N-1}C{sub 1}im][NTf{sub 2}]. A trend shift on the thermodynamic properties of vaporization along the alkyl side chains of the extended symmetric ionic liquids, around [C{sub 6}C{sub 6}im][NTf{sub 2}], was detected. An intensification of the odd-even effect was observed starting from [C{sub 6}C{sub 6}im][NTf{sub 2}], with higher enthalpies and entropies of vaporization for the odd numbered ionic liquids, [C{sub 7}C{sub 7}im][NTf{sub 2}] and [C{sub 9}C{sub 9}im][NTf{sub 2}]. Similar, but less pronounced, odd-even effect was found for the symmetric ionic liquids with lower alkyl side chains length, [C{sub N/2}C{sub N/2}im][NTf{sub 2}] (with N = 4, 6, 8, 10, and 12). This effect is related with the predominant orientation of the terminal methyl group of the alkyl chain to the imidazolium ring and their influence in the cation-anion interaction. The same Critical Alkyl length at the hexyl, (C{sub 6}C{sub 1}and C{sub 6}C{sub 6}) was found for both asymmetric and symmetric series indicating that the nanostructuration of the ionic liquids is related with alkyl chain length.« less

Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain

PubMed Central

Iwaniuk, Daniel P.; Whetmore, Eric D.; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian

2009-01-01

We report the synthesis and in vitro antimalarial activity of several new 4-amino-and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of P. falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11–15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain. PMID:19703776

Polymer composites containing nanotubes

NASA Technical Reports Server (NTRS)

Bley, Richard A. (Inventor)

2008-01-01

The present invention relates to polymer composite materials containing carbon nanotubes, particularly to those containing singled-walled nanotubes. The invention provides a polymer composite comprising one or more base polymers, one or more functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers and carbon nanotubes. The invention also relates to functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers, particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having side chain functionalization, and more particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having olefin side chains and alkyl epoxy side chains. The invention further relates to methods of making polymer composites comprising carbon nanotubes.

Empirical parameterization of a model for predicting peptide helix/coil equilibrium populations.

PubMed Central

Andersen, N. H.; Tong, H.

1997-01-01

A modification of the Lifson-Roig formulation of helix/coil transitions is presented; it (1) incorporates end-capping and coulombic (salt bridges, hydrogen bonding, and side-chain interactions with charged termini and the helix dipole) effects, (2) helix-stabilizing hydrophobic clustering, (3) allows for different inherent termination probabilities of individual residues, and (4) differentiates helix elongation in the first versus subsequent turns of a helix. Each residue is characterized by six parameters governing helix formation. The formulation of the conditional probability of helix initiation and termination that we developed is essentially the same as one presented previously (Shalongo W, Stellwagen, E. 1995. Protein Sci 4:1161-1166) and nearly the mathematical equivalent of the new capping formulation incorporated in the model presented by Rohl et al. (1996. Protein Sci 5:2623-2637). Side-chain/side-chain interactions are, in most cases, incorporated as context dependent modifications of propagation rather than nucleation parameters. An alternative procedure for converting [theta]221 values to experimental fractional helicities () is presented. Tests of the program predictions suggest this method may have some advantages both for designed peptides and for the analysis of secondary structure preferences that could drive the formation of molten-globule intermediates on protein folding pathways. The model predicts the fractional helicity of 385 peptides with a root-mean-square deviation (RMSD) of 0.050 and locates (with precise definition of the termini in many cases) helices in proteins as well as competing methods. The propagation and nucleation parameters were derived from NMR data and from the CD data for a 79 peptide "learning set" for which an excellent fit resulted (RMSD = 0.0295). The current set of parameter corrections for capping boxes, helix dipole interactions, and side-chain/side-chain interactions (coulombic, hydrogen bonding and hydrophobic clustering), although still under development provide a significant improvement in both helix/coil equilibrium prediction for peptides and helix location in protein sequences. This is clearly evident in the rms deviations between CD measures and calculated values of fractional helicity for different classes of peptides before and after applying the corrections: for peptides lacking capping boxes and i/i + 3 and i/i + 4 side-chain/side-chain interactions RMSD = 0.044 (n = 164) versus RMSD = 0.054 (0.172 without the corrections, n = 221) for peptides that required context-dependent corrections of the parameters. If we restrict the analysis to N-acylated peptides with helix stabilizing side-chain/side-chain interactions (including N-capping boxes), the degree to which our corrections account for the stabilizing interaction can be judged from the change in helicity underestimation, (calc-CD): -0.15 +/- 0.10, which is reduced to -0.018 +/- 0.048 (n = 191) upon applying the corrections. PMID:9300492

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS)☟

PubMed Central

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M.; Ioerger, Thomas R.; Burgess, Kevin

2013-01-01

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, “minimalist helical mimics”. It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i+4, i+7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i+3, i+7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds;(iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain “triads” in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the “side-chain correspondences” (eg i, i+4, i+7 or i, i+3, i+4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1 – 8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites. PMID:24121516

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

PubMed

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

2013-11-28

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1-8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites.

Device and method to relieve cordelle action in a chain driven pump

DOEpatents

Dysarz, Edward D.

1994-01-01

A cordelle action relief apparatus or device for use in sucker rod pumps in a petroleum or water well. The device is incorporated in a chain driven pump to prevent the chain from forming a bow or archlike configuration as the chain rolls off of the sprocket and down into the well. When the chain is allowed to form this bow or arch it could damage the well and well casing. The device includes a first rod on the side of the chain and a second rod on the second side of the chain that will allow the rollers of the chain to roll on the rod and further prevent the chain from bowing or arching and will further allow the rollers on the chain to roll on the rods which will further prevent damage to the well casing, the well, and the chain.

Dynamics of Polarons in Organic Conjugated Polymers with Side Radicals.

PubMed

Liu, J J; Wei, Z J; Zhang, Y L; Meng, Y; Di, B

2017-03-16

Based on the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model, and using the molecular dynamics method, we discuss the dynamics of electron and hole polarons propagating along a polymer chain, as a function of the distance between side radicals and the magnitude of the transfer integrals between the main chain and the side radicals. We first discuss the average velocities of electron and hole polarons as a function of the distance between side radicals. It is found that the average velocities of the electron polarons remain almost unchanged, while the average velocities of hole polarons decrease significantly when the radical distance is comparable to the polaron width. Second, we have found that the average velocities of electron polarons decrease with increasing transfer integral, but the average velocities of hole polarons increase. These results may provide a theoretical basis for understanding carriers transport properties in polymers chain with side radicals.

Highly Stable, Anion Conductive, Comb-Shaped Copolymers for Alkaline Fuel Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, NW; Leng, YJ; Hickner, MA

2013-07-10

To produce an anion-conductive and durable polymer electrolyte for alkaline fuel cell applications, a series of quaternized poly(2,6-dimethyl phenylene oxide)s containing long alkyl side chains pendant to the nitrogen-centered cation were synthesized using a Menshutkin reaction to form comb-shaped structures. The pendant alkyl chains were responsible for the development of highly conductive ionic domains, as confirmed by small-angle X-ray scattering (SAXS). The comb-shaped polymers having one alkyl side chain showed higher hydroxide conductivities than those with benzyltrimethyl ammonium moieties or structures with more than one alkyl side chain per cationic site. The highest conductivity was observed for comb-shaped polymers withmore » benzyldimethylhexadecyl ammonium cations. The chemical stabilities of the comb-shaped membranes were evaluated under severe, accelerated-aging conditions, and degradation was observed by measuring IEC and ion conductivity changes during aging. The comb-shaped membranes retained their high ion conductivity in 1 M NaOH at 80 degrees C for 2000 h. These cationic polymers were employed as ionomers in catalyst layers for alkaline fuel cells. The results indicated that the C-16 alkyl side chain ionomer had a slightly better initial performance, despite its low IEC value, but very poor durability in the fuel cell. In contrast, 90% of the initial performance was retained for the alkaline fuel cell with electrodes containing the C-6 side chain after 60 h of fuel cell operation.« less

In silico molecular engineering for a targeted replacement in a tumor-homing peptide

PubMed Central

Zanuy, David; Flores-Ortega, Alejandra; Jiménez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos; Nussinov, Ruth; Ruoslahti, Erkki; Alemán, Carlos

2009-01-01

A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg substitute has been investigated by a combination of simulated annealing and Molecular Dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone···backbone and side chain···side chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptide exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu and Lys side chains face the same side of the molecule, which is considered essential for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity. PMID:19432404

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase

PubMed Central

Gonzalez, Jeannette; Ramirez, Jennifer

2018-01-01

Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer’s and Huntington’s disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer’s disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (KI value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower KI value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding. PMID:27522651

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase.

PubMed

Gonzalez, Jeannette; Ramirez, Jennifer; Schwans, Jason P

2016-12-01

Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer's and Huntington's disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer's disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (K I value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower K I value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding.

A solid-state NMR study of the dynamics and interactions of phenylalanine rings in a statherin fragment bound to hydroxyapatite crystals.

PubMed

Gibson, James M; Popham, Jennifer M; Raghunathan, Vinodhkumar; Stayton, Patrick S; Drobny, Gary P

2006-04-26

Extracellular matrix proteins regulate hard tissue growth by acting as adhesion sites for cells, by triggering cell signaling pathways, and by directly regulating the primary and/or secondary crystallization of hydroxyapatite, the mineral component of bone and teeth. Despite the key role that these proteins play in the regulation of hard tissue growth in humans, the exact mechanism used by these proteins to recognize mineral surfaces is poorly understood. Interactions between mineral surfaces and proteins very likely involve specific contacts between the lattice and the protein side chains, so elucidation of the nature of interactions between protein side chains and their corresponding inorganic mineral surfaces will provide insight into the recognition and regulation of hard tissue growth. Isotropic chemical shifts, chemical shift anisotropies (CSAs), NMR line-width information, (13)C rotating frame relaxation measurements, as well as direct detection of correlations between (13)C spins on protein side chains and (31)P spins in the crystal surface with REDOR NMR show that, in the peptide fragment derived from the N-terminal 15 amino acids of salivary statherin (i.e., SN-15), the side chain of the phenylalanine nearest the C-terminus of the peptide (F14) is dynamically constrained and oriented near the surface, whereas the side chain of the phenylalanine located nearest to the peptide's N-terminus (F7) is more mobile and is oriented away from the hydroxyapatite surface. The relative dynamics and proximities of F7 and F14 to the surface together with prior data obtained for the side chain of SN-15's unique lysine (i.e., K6) were used to construct a new picture for the structure of the surface-bound peptide and its orientation to the crystal surface.

Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the HDL receptor SR-BI

PubMed Central

Yu, Miao; Lau, Thomas Y.; Carr, Steven A.; Krieger, Monty

2013-01-01

The high density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys321-Pro322-Cys323 (CPC) motif and connect Cys280 to Cys334. We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys384 to HDL binding and lipid uptake. The effects of CPC mutations on activity were context dependent. Full wild-type (WT) activity required Pro322 and Cys323 only when Cys321 was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX or XXX mutants (X≠WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys323 is deleterious, perhaps because of aberrant disulfide bond formation. Pro322 may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for activity. C384X (X=S,T,L,Y,G,A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (increased binding, decreased uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C384X mutants were BLT-1 resistant, supporting the proposal that Cys384's thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories. PMID:23205738

Atoms-in-molecules study of the genetically encoded amino acids. III. Bond and atomic properties and their correlations with experiment including mutation-induced changes in protein stability and genetic coding.

PubMed

Matta, Chérif F; Bader, Richard F W

2003-08-15

This article presents a study of the molecular charge distributions of the genetically encoded amino acids (AA), one that builds on the previous determination of their equilibrium geometries and the demonstrated transferability of their common geometrical parameters. The properties of the charge distributions are characterized and given quantitative expression in terms of the bond and atomic properties determined within the quantum theory of atoms-in-molecules (QTAIM) that defines atoms and bonds in terms of the observable charge density. The properties so defined are demonstrated to be remarkably transferable, a reflection of the underlying transferability of the charge distributions of the main chain and other groups common to the AA. The use of the atomic properties in obtaining an understanding of the biological functions of the AA, whether free or bound in a polypeptide, is demonstrated by the excellent statistical correlations they yield with experimental physicochemical properties. A property of the AA side chains of particular importance is the charge separation index (CSI), a quantity previously defined as the sum of the magnitudes of the atomic charges and which measures the degree of separation of positive and negative charges in the side chain of interest. The CSI values provide a correlation with the measured free energies of transfer of capped side chain analogues, from the vapor phase to aqueous solution, yielding a linear regression equation with r2 = 0.94. The atomic volume is defined by the van der Waals isodensity surface and it, together with the CSI, which accounts for the electrostriction of the solvent, yield a linear regression (r2 = 0.98) with the measured partial molar volumes of the AAs. The changes in free energies of transfer from octanol to water upon interchanging 153 pairs of AAs and from cyclohexane to water upon interchanging 190 pairs of AAs, were modeled using only three calculated parameters (representing electrostatic and volume contributions) yielding linear regressions with r2 values of 0.78 and 0.89, respectively. These results are a prelude to the single-site mutation-induced changes in the stabilities of two typical proteins: ubiquitin and staphylococcal nuclease. Strong quadratic correlations (r2 approximately 0.9) were obtained between DeltaCSI upon mutation and each of the two terms DeltaDeltaH and TDeltaDeltaS taken from recent and accurate differential scanning calorimetry experiments on ubiquitin. When the two terms are summed to yield DeltaDeltaG, the quadratic terms nearly cancel, and the result is a simple linear fit between DeltaDeltaG and DeltaCSI with r2 = 0.88. As another example, the change in the stability of staphylococcal nuclease upon mutation has been fitted linearly (r2 = 0.83) to the sum of a DeltaCSI term and a term representing the change in the van der Waals volume of the side chains upon mutation. The suggested correlation of the polarity of the side chain with the second letter of the AA triplet genetic codon is given concrete expression in a classification of the side chains in terms of their CSI values and their group dipole moments. For example, all amino acids with a pyrimidine base as their second letter in mRNA possess side-chain CSI < or = 2.8 (with the exception of Cys), whereas all those with CSI > 2.8 possess an purine base. The article concludes with two proposals for measuring and predicting molecular complementarity: van der Waals complementarity expressed in terms of the van der Waals isodensity surface and Lewis complementarity expressed in terms of the local charge concentrations and depletions defined by the topology of the Laplacian of the electron density. A display of the experimentally accessible Laplacian distribution for a folded protein would offer a clear picture of the operation of the "stereochemical code" proposed as the determinant in the folding process. Copyright 2003 Wiley-Liss, Inc.

Precise side-chain conformation analysis of L-phenylalanine in α-helical polypeptide by quantum-chemical calculation and 13C CP-MAS NMR measurement

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Suzuki, Junya; Kurosu, Hiromichi; Yamanobe, Takeshi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a well-defined α-helical octadecapeptide composed of L-alanine (Ala) and L-phenylalanine (Phe) residues, H-(Ala) 8-Phe-(Ala) 9-OH, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy and the precise secondary structural parameters such as main-chain dihedral angles and hydrogen-bond parameters of the optimized structure, we confirmed that the conformational stability of an α-helix is affected dominantly by the side-chain conformation ( χ1) of the Phe residue in this system: model A ( T form: around 180° of χ1) is most stable in α-helix and model B ( G + form: around -60° of χ1) is next stable, but model C ( G - form: around 60° of χ1) is less stable. In addition, we demonstrate that the stable conformation of poly( L-phenylalanine) is an α-helix with the side-chain T form, by comparison of the carbonyl 13C chemical shift measured by 13C CP-MAS NMR and the calculated one.

Synthesis and Characterization of Itaconic Anhydride and Stearyl Methacrylate Copolymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang, S.; Huang, S; Weiss, R

The free-radical copolymerization and the properties of comb-like copolymers derived from renewable resources, itaconic anhydride (ITA) and stearyl methacrylate (SM), are described. The ITA-SM copolymers were nearly random with a slight alternating tendency. The copolymers exhibited a nanophase-separated morphology, with the stearate side-chains forming a bilayer, semi-crystalline structure. The melting point (Tm) of the side-chains and the crystallinity decreased with increasing ITA concentration. The crystalline side-chains suppressed molecular motion of the main chain, so that a glass transition temperature (Tg) was not resolved unless the ITA concentration was sufficiently high so that Tg > Tm. The softening point and modulusmore » of the copolymers increased with the increasing ITA concentration, but the thermal stability decreased.« less

Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies.

PubMed

Lavrado, João; Cabal, Ghislain G; Prudêncio, Miguel; Mota, Maria M; Gut, Jiri; Rosenthal, Philip J; Díaz, Cecília; Guedes, Rita C; dos Santos, Daniel J V A; Bichenkova, Elena; Douglas, Kenneth T; Moreira, Rui; Paulo, Alexandra

2011-02-10

The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial and cytotoxicity properties are reported. Propyl, butyl, and cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing cytotoxicity when compared with the parent compound. Localization studies inside parasite blood stages by fluorescence microscopy showed that these derivatives accumulate inside the nucleus, indicating that the incorporation of a basic side chain is not sufficient enough to promote selective accumulation in the acidic digestive vacuole of the parasite. Most of the compounds within this series showed the ability to bind to a double-stranded DNA duplex as well to monomeric hematin, suggesting that these are possible targets associated with the observed antimalarial activity. Overall, these novel cryptolepine analogues with substantially improved antiplasmodial activity and selectivity index provide a promising starting point for development of potent and highly selective agents against drug-resistant malaria parasites.

From Semi- to Full-Two-Dimensional Conjugated Side-Chain Design: A Way toward Comprehensive Solar Energy Absorption

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Pengjie; Wang, Huan; Qu, Shiwei

Two polymers with fully two-dimensional (2D) conjugated side chains, 2D-PTB-Th and 2D-PTB-TTh, were synthesized and characterized through simultaneously integrating the 2D-TT and the 2D-BDT monomers onto the polymer backbone. Resulting from the synergistic effect from the conjugated side chains on both monomers, the two polymers showed remarkably efficient absorption of the sunlight and improved pi-pi intermolecular interactions for efficient charge carrier transport. The optimized bulk heterojunction device based on 2D-PTB-Th and PC71BM shows a higher PCE of 9.13% compared to PTB7-Th with a PCE of 8.26%, which corresponds to an approximately 10% improvement in solar energy conversion. The fully 2D-conjugatedmore » side-chain concept reported here developed a new molecular design strategy for polymer materials with enhanced sunlight absorption and efficient solar energy conversion.« less

Novel pleuromutilin derivatives with excellent antibacterial activity against Staphylococcus aureus.

PubMed

Xu, Peng; Zhang, Yuan-Yuan; Sun, Yong-Xue; Liu, Jian-Hua; Yang, Bing; Wang, Yu-Zhong; Wang, Yu-Liang

2009-06-01

Ten novel pleuromutilin derivatives with thioether moiety and heterocyclic carboxamide or chloroformate group in the side chain were synthesized and confirmed by (1)H NMR, IR and HRMS. The results of the antibacterial activity showed that the title compounds had excellent antibacterial activity against Staphylococcus aureus, among which the MIC of 5f reached 0.03125 microg/mL.

Total synthesis of (+)-antroquinonol and (+)-antroquinonol D.

PubMed

Sulake, Rohidas S; Chen, Chinpiao

2015-03-06

The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate.

The Synthesis of a Dipeptide from its Component Amino Acids: Protecting Groups in the Elementary Organic Laboratory.

ERIC Educational Resources Information Center

Young, Paul E.; Campbell, Andrew

1982-01-01

A simple, three-step procedure for synthesizing a dipeptide from its component amino acids is described. The dipeptide synthesized uses inexpensive amino acids having hydrocarbon side-chains and can be observed in E/Z forms by nuclear magnetic resonance spectroscopy. Each step in the synthesis produces white crystalline products using standard…

Can collision-induced negative-ion fragmentations of [M-H](-) anions be used to identify phosphorylation sites in peptides?

PubMed

Tran, T T Nha; Wang, Tianfang; Hack, Sandra; Hoffmann, Peter; Bowie, John H

2011-12-15

A joint experimental and theoretical investigation of the fragmentation behaviour of energised [M-H](-) anions from selected phosphorylated peptides has confirmed some of the most complex rearrangement processes yet to be reported for peptide negative ions. In particular: pSer and pThr (like pTyr) may transfer phosphate groups to C-terminal carboxyl anions and to the carboxyl anion side chains of Asp and Glu, and characteristic nucleophilic/cleavage reactions accompany or follow these rearrangements. pTyr may transfer phosphate to the side chains of Ser and Thr. The reverse reaction, namely transfer of a phosphate group from pSer or pThr to Tyr, is energetically unfavourable in comparison. pSer can transfer phosphate to a non-phosphorylated Ser. The non-rearranged [M-H](-) species yields more abundant product anions than its rearranged counterpart. If a peptide containing any or all of Ser, Thr and Tyr is not completely phosphorylated, negative-ion cleavages can determine the number of phosphated residues, and normally the positions of Ser, Thr and Tyr, but not which specific residues are phosphorylated. This is in accord with comments made earlier by Lehmann and coworkers. Copyright © 2011 John Wiley & Sons, Ltd.

Multidrug resistance-selective antiproliferative activity of Piper amide alkaloids and synthetic analogues.

PubMed

Wang, Yue-Hu; Goto, Masuo; Wang, Li-Ting; Hsieh, Kan-Yen; Morris-Natschke, Susan L; Tang, Gui-Hua; Long, Chun-Lin; Lee, Kuo-Hsiung

2014-10-15

Twenty-five amide alkaloids (1-25) from Piper boehmeriifolium and 10 synthetic amide alkaloid derivatives (39-48) were evaluated for antiproliferative activity against eight human tumor cell lines, including chemosensitive and multidrug-resistant (MDR) cell lines. The results suggested tumor type-selectivity. 1-[7-(3,4,5-Trimethoxyphenyl)heptanoyl]piperidine (46) exhibited the best inhibitory activity (IC50=4.94 μM) against the P-glycoprotein (P-gp)-overexpressing KBvin MDR sub-line, while it and all other tested compounds, except 9, were inactive (IC50 >40 μM) against MDA-MB-231 and SK-BR-3. Structure-activity relationships (SARs) indicated that (i) 3,4,5-trimethoxy phenyl substitution is critical for selectivity against KBvin, (ii) the 4-methoxy group in this pattern is crucial for antiproliferative activity, (iii) double bonds in the side chain are not needed for activity, and (iv), in arylalkenylacyl amide alkaloids, replacement of an isobutylamino group with pyrrolidin-1-yl or piperidin-1-yl significantly improved activity. Further study on Piper amides is warranted, particularly whether side chain length affects the ability to overcome the MDR cancer phenotype. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure of Chlorobium tepidum sepiapterin reductase complex reveals the novel substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin.

PubMed

Supangat, Supangat; Seo, Kyung Hye; Choi, Yong Kee; Park, Young Shik; Son, Daeyoung; Han, Chang-deok; Lee, Kon Ho

2006-01-27

Sepiapterin reductase (SR) is involved in the last step of tetrahydrobiopterin (BH(4)) biosynthesis by reducing the di-keto group of 6-pyruvoyl tetrahydropterin. Chlorobium tepidum SR (cSR) generates a distinct BH(4) product, L-threo-BH(4) (6R-(1'S,2'S)-5,6,7,8-BH(4)), whereas animal enzymes produce L-erythro-BH(4) (6R-(1'R,2'S)-5,6,7,8-BH(4)) although it has high amino acid sequence similarities to the other animal enzymes. To elucidate the structural basis for the different reaction stereospecificities, we have determined the three-dimensional structures of cSR alone and complexed with NADP and sepiapterin at 2.1 and 1.7 A resolution, respectively. The overall folding of the cSR, the binding site for the cofactor NADP(H), and the positions of active site residues were quite similar to the mouse and the human SR. However, significant differences were found in the substrate binding region of the cSR. In comparison to the mouse SR complex, the sepiapterin in the cSR is rotated about 180 degrees around the active site and bound between two aromatic side chains of Trp-196 and Phe-99 so that its pterin ring is shifted to the opposite side, but its side chain position is not changed. The swiveled sepiapterin binding results in the conversion of the side chain configuration, exposing the opposite face for hydride transfer from NADPH. The different sepiapterin binding mode within the conserved catalytic architecture presents a novel strategy of switching the reaction stereospecificities in the same protein fold.

Block and Graft Copolymers of Polyhydroxyalkanoates

NASA Astrophysics Data System (ADS)

Marchessault, Robert H.; Ravenelle, François; Kawada, Jumpei

2004-03-01

Polyhydroxyalkanoates (PHAs) were modified for diblock copolymer and graft polymer by catalyzed transesterification in the melt and by chemical synthesis to extend the side chains of the PHAs, and the polymers were studied by transmission electron microscopy (TEM) X-ray diffraction, thermal analysis and nuclear magnetic resonance (NMR). Catalyzed transesterification in the melt is used to produce diblock copolymers of poly[3-hydroxybutyrate] (PHB) and monomethoxy poly[ethylene glycol] (mPEG) in a one-step process. The resulting diblock copolymers are amphiphilic and self-assemble into sterically stabilized colloidal suspensions of PHB crystalline lamellae. Graft polymer was synthesized in a two-step chemical synthesis from biosynthesized poly[3-hydroxyoctanoate-co-3-hydroxyundecenoate] (PHOU) containing ca. 25 mol chains. 11-mercaptoundecanoic acid reacts with the side chain alkenes of PHOU by the radical addition creating thioether linkage with terminal carboxyl functionalities. The latter groups were subsequently transformed into the amide or ester linkage by tridecylamine or octadecanol, respectively, producing new graft polymers. The polymers have different physical properties than poly[3-hydroxyoctanoate] (PHO) which is the main component of the PHOU, such as non-stickiness and higher thermal stability. The combination of biosynthesis and chemical synthesis produces a hybrid thermoplastic elastomer with partial biodegradability.

Nacre-mimetic clay/xyloglucan bionanocomposites: a chemical modification route for hygromechanical performance at high humidity.

PubMed

Kochumalayil, Joby J; Morimune, Seira; Nishino, Takashi; Ikkala, Olli; Walther, Andreas; Berglund, Lars A

2013-11-11

Nacre-mimetic bionanocomposites of high montmorillonite (MTM) clay content, prepared from hydrocolloidal suspensions, suffer from reduced strength and stiffness at high relative humidity. We address this problem by chemical modification of xyloglucan in (XG)/MTM nacre-mimetic nanocomposites, by subjecting the XG to regioselective periodate oxidation of side chains to enable it to form covalent cross-links to hydroxyl groups in neighboring XG chains or to the MTM surface. The resulting materials are analyzed by FTIR spectroscopy, thermogravimetric analysis, carbohydrate analysis, calorimetry, X-ray diffraction, scanning electron microscopy, tensile tests, and oxygen barrier properties. We compare the resulting mechanical properties at low and high relative humidity. The periodate oxidation leads to a strong increase in modulus and strength of the materials. A modulus of 30 GPa for cross-linked composite at 50% relative humidity compared with 13.7 GPa for neat XG/MTM demonstrates that periodate oxidation of the XG side chains leads to crucially improved stress transfer at the XG/MTM interface, possibly through covalent bond formation. This enhanced interfacial adhesion and internal cross-linking of the matrix moreover preserves the mechanical properties at high humidity condition and leads to a Young's modulus of 21 GPa at 90%RH.

Ionic-Liquid-Infused Nanostructures as Repellent Surfaces.

PubMed

Galvan, Yaraset; Phillips, Katherine R; Haumann, Marco; Wasserscheid, Peter; Zarraga, Ramon; Vogel, Nicolas

2018-06-12

In order to prepare lubricant-infused repellent coatings on silica nanostructures using low vapor pressure ionic liquids as lubricants, we study the wetting behavior of a set of imidazolium-based ionic liquids with different alkyl side chains as a function of the applied surface functionalities. We take advantage of the structural color of inverse opals prepared from a colloidal coassembly technique to study the infiltration of ionic liquids into these nanoporous structures. We find that the more hydrophobic ionic liquids with butyl and hexyl side chains can completely infiltrate inverse opals functionalized with mixed self-assembled monolayers composed of imidazole groups and aliphatic hydrocarbon chains, which we introduce via silane chemistry. These molecular species reflect the chemical nature of the ionic liquid, thereby increasing the affinity between the liquid and solid surface. The mixed surface chemistry provides sufficiently small contact angles with the ionic liquid to infiltrate the nanopores while maximizing the contact angle with water. As a result, the mixed monolayers enable the design of a stable ionic liquid/solid interface that is able to repel water as a test liquid. Our results underline the importance of matching chemical affinities to predict and control the wetting behavior in complex, multiphase systems.

Conformational profile of a proline-arginine hybrid

PubMed Central

Revilla-López, Guillermo; Jiménez, Ana I.; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-01-01

The intrinsic conformational preferences of a new non-proteinogenic amino acid have been explored by computational methods. This tailored molecule, named (βPro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the Cβ position of the five-membered pyrrolidine ring, either in a cis or a trans orientation with respect to the carboxylic acid. The conformational profile of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of (βPro)Arg has been examined in the gas phase and in solution by B3LYP/6–31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen-bonds. Thus, both cis and trans (βPro)Arg exhibit a preference for the αL conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups. PMID:20886854

Conformational profile of a proline-arginine hybrid.

PubMed

Revilla-López, Guillermo; Jiménez, Ana I; Cativiela, Carlos; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

2010-10-25

The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named ((β)Pro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C(β) position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of ((β)Pro)Arg have been examined in the gas phase and in solution by B3LYP/6-31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-((β)Pro)Arg exhibit a preference for the α(L) conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.

Structural properties of atactic polystyrene adsorbed onto solid surfaces.

PubMed

Tatek, Yergou B; Tsige, Mesfin

2011-11-07

In the present work, we are studying the local conformation of chains in a thin film of polystyrene adsorbed on a solid substrate by using atomistically detailed simulations. The simulations are carried out by using the readily available and massively parallel molecular dynamics code known as LAMMPS. In particular, a special emphasis is given to the density and orientation of side chains (which consist of phenyl groups and methylene units) at solid/polymer and polymer/vacuum interfaces. Three types of substrates were used in our study: α-quartz, graphite, and amorphous silica. Our investigation was restricted to atactic polystyrene. Our results show that the density and structural properties of side chains depend on the type of surface. An excess of phenyl rings is observed near the α-quartz substrate while the film adsorbed on graphite is depleted in C(6)H(5). Moreover, the orientation of the rings and methylene units on the substrate/film interface show a strong dependence on the type of the substrate, while the rings at the film/vacuum interface show a marked tendency to point outward, away from the film. The results we obtained are in a large part in good agreement with previous experimental and simulation results.

Molecular dynamics study of linear and comb-like polyelectrolytes in aqueous solution: effect of Ca2+ ions

NASA Astrophysics Data System (ADS)

Tong, Kefeng; Song, Xingfu; Sun, Shuying; Xu, Yanxia; Yu, Jianguo

2014-08-01

All-atom molecular dynamics simulations were employed to provide microscopic mechanism for the salt tolerance of polyelectrolytes dispersants. The conformational variation of polyelectrolytes and interactions between COO- groups and counterions/water molecules were also studied via radius of gyration and pair correlations functions. Sodium polyacrylate (NaPA) and sodium salts of poly(acrylic acid)-poly(ethylene oxide) (NaPA-PEO) were selected as the representative linear and comb-like polyelectrolyte, respectively. The results show that Ca2+ ions interact with COO- groups much stronger than Na+ ions and can bring ion-bridging interaction between intermolecular COO- groups in the NaPA systems. While in the NaPA-PEO systems, the introduced PEO side chains can prevent backbone chains from ion-bridging interactions and weaken the conformational changes. The present results can help in selecting and designing new-type efficient polyelectrolyte dispersants with good salt tolerance.

Transport of triplet excitons along continuous 100 nm polyfluorene chains

DOE PAGES

Xi, Liang; Bird, Matthew; Mauro, Gina; ...

2014-12-03

Triplet excitons created in poly-2,7-(9,9-dihexyl)fluorene (pF) chains with end trap groups in solution are efficiently transported to and captured by the end groups. The triplets explore the entire lengths of the chains, even for ~100 nm long chains enabling determination of the completeness of end capping. The results show that the chains continuous: they may contain transient barriers or traps, such as those from fluctuations of dihedral angles, but are free of major defects that stop motion of the triplets. Quantitative determinations are aided by the addition of a strong electron donor, TMPD, which removes absorption bands of the end-trappedmore » triplets. For chains having at least one end trap, triplet capture is quantitative on the 1 µs timescale imposed by the use of the donor. Fractions of chains having no end traps were 0.15 for pF samples with anthraquinone (AQ) end traps and 0.063 with naphthylimide (NI) end traps. These determinations agreed with measurements by NMR for short (<40 polymer repeat units (PRU)) chains, where NMR determinations are accurate. The results find no evidence for traps or barriers to transport of triplets, and places limits on the possible presence of defects as impenetrable barriers to less than one per 300 PRU. The present results present a paradigm different from the current consensus, derived from observations of singlet excitons, that conjugated chains are divided into “segments,” perhaps by some kind of defects. For the present pF chains, the segmentation either does not apply to triplet excitons or is transient so that the defects are healed or surmounted in times much shorter than 1 µs. Triplets on chains without end trap groups transfer to chains with end traps on a slower time scale. Rate constants for these bimolecular triplet transfer reactions were found to increase with the length of the accepting chain, as did rate constants for triplet transfer to the chains from small molecules like biphenyl. As a result, a second set of polyfluorenes with 2-butyloctyl side chains was found to have a much lower completeness of end capping.« less

Structural Basis for Bc12-Regulated Mitochondrion-Dependent Apoptosis

DTIC Science & Technology

2005-04-01

groups , double-resonance (’H/15N or 1H/ 31P) probes had square r.f. which have a considerably narrower ’IN chemical shift coils wrapped directly around...bilayers, which provides no res- B E H olution [Fig. 5(D)]. The peak near 35 ppm results from the amino groups of the lysine side-chains and the N...tissue-specific and physiological state-specific sub- 21. Huang Q, Petros AM, Virgin HW, Fesik SW, Olejniczak ET. Proc. units of the Na+, K+-ATPase. The

4-Meth-oxy-3-(meth-oxy-meth-yl)benzalde-hyde.

PubMed

Zhang, Jing-Chao; Sun, Jun; Zhang, Juan; Liu, Guang-Lin; Guo, Cheng

2013-01-01

In the title compound, C10H12O3, the dihedral angle between the benzene ring and the meth-oxy-methyl side chain is 9.7 (2)°. The O atom of the aldehyde group and the C atom of the meth-oxy group deviate from the plane of the ring by 0.039 (3) and 0.338 (4) Å, respectively. The only inter-molecular inter-actions are very weak C-H⋯π inter-actions.

Molecular Mechanism Responsible for Reentrance to Ia3d Gyroid Phase in Cubic Mesogen BABH(n)

NASA Astrophysics Data System (ADS)

Nakazawa, Yuri; Yamamura, Yasuhisa; Kutsumizu, Shoichi; Saito, Kazuya

2012-09-01

Maximum entropy analyses of small-angle X-ray diffraction patterns of a series of title compounds [1,2-bis(4'-n-alkyloxybenzoyl)hydrazine, n: number of carbon atoms in an alkyl group] yield a new description of the so-called gyroid phase. The structure is described as two sets of connected triangles, instead of jungle gyms consisting of rods, embedded in two spaces separated by a mathematical gyroid. The reconstructed electron density provides new evidence of molecular packing: While molecules having short alkyl chains laterally aggregate to form single layers of triangular shape with nearly vertical alignments, those with long chains split into two groups on both sides of the triangular planes. The formation of double layers of the molecular cores is tolerable with the possible formation of hydrogen bonds between shifted molecules, and adjusts the volume fraction of the core part to attain the stability of the reentrant gyroid phase upon chain elongation.

The effects of 6-week training programs on throwing accuracy, proprioception, and core endurance in baseball.

PubMed

Lust, Kathleen R; Sandrey, Michelle A; Bulger, Sean M; Wilder, Nathan

2009-08-01

With a limited number of outcomes-based studies, only recommendations for strength-training and rehabilitation programs can be made. To determine the extent to which throwing accuracy, core stability, and proprioception improved after completion of a 6-week training program that included open kinetic chain (OKC), closed kinetic chain (CKC), and/or core-stability exercises. A 2 x 3 factorial design. Division III college. 19 healthy baseball athletes with a control group of 15. Two 6-week programs including OKC, CKC, and core-stabilization exercises that were progressed each week. Functional throwing-performance index, closed kinetic chain upper extremity stability test, back-extensor test, 45 degrees abdominal-fatigue test, and right- and left-side bridging test. There was no significant difference between groups. An increase was evident in all pretest-to-posttest results, with improvement ranging from 1.36% to 140%. Both of the 6-week training programs could be used to increase throwing accuracy, core stability, and proprioception in baseball.

Molecular design of anti-MRSA agents based on the anacardic acid scaffold.

PubMed

Green, Ivan R; Tocoli, Felismino E; Lee, Sang Hwa; Nihei, Ken-Ichi; Kubo, Isao

2007-09-15

A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6-(4',8'-dimethylnonyl)salicylic acid, and the alicyclic side-chain analogue, 6-cyclododecylmethyl salicylic acid, with the minimum inhibitory concentration (MIC) of 0.39 microg/mL, respectively. This activity was superior to that of the most potent antibacterial anacardic acid isolated from the cashew Anacardium occidentale (Anacardiaceae), apple and nut, that is, the 6-[8'(Z),11'(Z),14'-pentadecatrienyl]salicylic acid.

Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain.

PubMed

Nakajima, Ryo; Yamamoto, Naoshi; Hirayama, Shigeto; Iwai, Takashi; Saitoh, Akiyoshi; Nagumo, Yasuyuki; Fujii, Hideaki; Nagase, Hiroshi

2015-10-01

We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a β-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine. Copyright © 2015 Elsevier Ltd. All rights reserved.

BetaSCPWeb: side-chain prediction for protein structures using Voronoi diagrams and geometry prioritization

PubMed Central

Ryu, Joonghyun; Lee, Mokwon; Cha, Jehyun; Laskowski, Roman A.; Ryu, Seong Eon; Kim, Deok-Soo

2016-01-01

Many applications, such as protein design, homology modeling, flexible docking, etc. require the prediction of a protein's optimal side-chain conformations from just its amino acid sequence and backbone structure. Side-chain prediction (SCP) is an NP-hard energy minimization problem. Here, we present BetaSCPWeb which efficiently computes a conformation close to optimal using a geometry-prioritization method based on the Voronoi diagram of spherical atoms. Its outputs are visual, textual and PDB file format. The web server is free and open to all users at http://voronoi.hanyang.ac.kr/betascpweb with no login requirement. PMID:27151195

Molybdoenzyme That Catalyzes the Anaerobic Hydroxylation of a Tertiary Carbon Atom in the Side Chain of Cholesterol*

PubMed Central

Dermer, Juri; Fuchs, Georg

2012-01-01

Cholesterol is a ubiquitous hydrocarbon compound that can serve as substrate for microbial growth. This steroid and related cyclic compounds are recalcitrant due to their low solubility in water, complex ring structure, the presence of quaternary carbon atoms, and the low number of functional groups. Aerobic metabolism therefore makes use of reactive molecular oxygen as co-substrate of oxygenases to hydroxylate and cleave the sterane ring system. Consequently, anaerobic metabolism must substitute oxygenase-catalyzed steps by O2-independent hydroxylases. Here we show that one of the initial reactions of anaerobic cholesterol metabolism in the β-proteobacterium Sterolibacterium denitrificans is catalyzed by an unprecedented enzyme that hydroxylates the tertiary C25 atom of the side chain without molecular oxygen forming a tertiary alcohol. This steroid C25 dehydrogenase belongs to the dimethyl sulfoxide dehydrogenase molybdoenzyme family, the closest relative being ethylbenzene dehydrogenase. It is a heterotrimer, which is probably located at the periplasmic side of the membrane and contains one molybdenum cofactor, five [Fe-S] clusters, and one heme b. The draft genome of the organism contains several genes coding for related enzymes that probably replace oxygenases in steroid metabolism. PMID:22942275

Total synthesis of a CD-ring: side-chain building block for preparing 17-epi-calcitriol derivatives from the Hajos-Parrish dione.

PubMed

Michalak, Karol; Wicha, Jerzy

2011-08-19

An efficient synthesis of the key building block for 17-epi-calctriol from the Hajos-Parrish dione involving a sequence of diastereoselective transformation of the azulene core and the side-chain construction is presented.

Conformational Changes of Bovine Serum Albumin Induced by Adsorption on Different Clay Surfaces: FTIR Analysis.

PubMed

Servagent-Noinville; Revault; Quiquampoix; Baron

2000-01-15

Interactions between proteins and clays perturb biological activity in ecosystems, particularly soil extracellular enzyme activity. The pH dependence of hydrophobic, hydrophilic, and electrostatic interactions on the adsorption of bovine serum albumin (BSA) is studied. BSA secondary structures and hydration are revealed from computation of the Amide I and II FTIR absorption profiles. The influence of ionization of Asp, Glu, and His side chains on the adsorption processes is deduced from correlation between p(2)H dependent carboxylic/carboxylate ratio and Amide band profiles. We quantify p(2)H dependent internal and external structural unfolding for BSA adsorbed on montmorillonite, which is an electronegative phyllosilicate. Adsorption on talc, a hydrophobic surface, is less denaturing. The results emphasize the importance of electrostatic interactions in both adsorption processes. In the first case, charged side chains directly influence BSA adsorption that generate the structural transition. In the second case, the forces that attract hydrophobic side chains toward the protein-clay interface are large enough to distort peripheral amphiphilic helical domains. The resulting local unfolding displaces enough internal ionized side chains to prevent them from establishing salt bridges as for BSA native structure in solution. On montmorillonite, a particular feature is a higher protonation of the Asp and Glu side chains of the adsorbed BSA than in solution, which decreases coulombic repulsion. Copyright 2000 Academic Press.

Protein side chain rotational isomerization: A minimum perturbation mapping study

NASA Astrophysics Data System (ADS)

Haydock, Christopher

1993-05-01

A theory of the rotational isomerization of the indole side chain of tryptophan-47 of variant-3 scorpion neurotoxin is presented. The isomerization potential energy, entropic part of the isomerization free energy, isomer probabilities, transition state theory reaction rates, and indole order parameters are calculated from a minimum perturbation mapping over tryptophan-47 χ1×χ2 torsion space. A new method for calculating the fluorescence anisotropy from molecular dynamics simulations is proposed. The method is based on an expansion that separates transition dipole orientation from chromophore dynamics. The minimum perturbation potential energy map is inverted and applied as a bias potential for a 100 ns umbrella sampling simulation. The entropic part of the isomerization free energy as calculated by minimum perturbation mapping and umbrella sampling are in fairly close agreement. Throughout, the approximation is made that two glutamine and three tyrosine side chains neighboring tryptophan-47 are truncated at the Cβ atom. Comparison with the previous combination thermodynamic perturbation and umbrella sampling study suggests that this truncated neighbor side chain approximation leads to at least a qualitatively correct theory of tryptophan-47 rotational isomerization in the wild type variant-3 scorpion neurotoxin. Analysis of van der Waals interactions in a transition state region indicates that for the simulation of barrier crossing trajectories a linear combination of three specially defined dihedral angles will be superior to a simple side chain dihedral reaction coordinate.

Caution Is Required in Interpretation of Mutations in the Voltage Sensing Domain of Voltage Gated Channels as Evidence for Gating Mechanisms

PubMed Central

Kariev, Alisher M.; Green, Michael E.

2015-01-01

The gating mechanism of voltage sensitive ion channels is generally considered to be the motion of the S4 transmembrane segment of the voltage sensing domains (VSD). The primary supporting evidence came from R→C mutations on the S4 transmembrane segment of the VSD, followed by reaction with a methanethiosulfonate (MTS) reagent. The cys side chain is –SH (reactive form –S−); the arginine side chain is much larger, leaving space big enough to accommodate the MTS sulfonate head group. The cavity created by the mutation has space for up to seven more water molecules than were present in wild type, which could be displaced irreversibly by the MTS reagent. Our quantum calculations show there is major reorientation of three aromatic residues that face into the cavity in response to proton displacement within the VSD. Two phenylalanines reorient sufficiently to shield/unshield the cysteine from the intracellular and extracellular ends, depending on the proton positions, and a tyrosine forms a hydrogen bond to the cysteine sulfur with its side chain –OH. These could produce the results of the experiments that have been interpreted as evidence for physical motion of the S4 segment, without physical motion of the S4 backbone. The computations strongly suggest that the interpretation of cysteine substitution reaction experiments be re-examined in the light of these considerations. PMID:25588216

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qasim, Mohammad A., E-mail: qasimm@ipfw.edu; Song, Jikui; Markley, John L.

Research highlights: {yields} Large pK shifts in ionizable groups when buried in the protein interior. {yields} Substrate dependent shifts in pH optimum for serine proteases. {yields} Lys side chain is a stronger acid in serine protease S{sub 1} pocket than Asp side chain. -- Abstract: Enzymatic hydrolysis of the synthetic substrate succinyl-Ala-Ala-Pro-Xxx-pNA (where Xxx = Leu, Asp or Lys) catalyzed by bovine chymotrypsin (CHYM) or Streptomyces griseus protease B (SGPB) has been studied at different pH values in the pH range 3-11. The pH optima for substrates having Leu, Asp, and Lys have been found to be 7.5-8.0, 5.5-6.0, andmore » {approx}10, respectively. At the normally reported pH optimum (pH 7-8) of CHYM and SGPB, the substrate with Leu at the reactive site is more than 25,000-fold more reactive than that with Asp. However, when fully protonated, Asp is nearly as good a substrate as Leu. The pK values of the side chains of Asp and Lys in the hydrophobic S{sub 1} pocket of CHYM and SGPB have been calculated from pH-dependent hydrolysis data and have been found to be about 9 for Asp and 7.4 and 9.7 for Lys for CHYM and SGPB, respectively. The results presented in this communication suggest a possible application of CHYM like enzymes in cleaving peptide bonds contributed by acidic amino acids between pH 5 and 6.« less

Side chain variations radically alter the diffusion of poly(2-alkyl-2-oxazoline) functionalised nanoparticles through a mucosal barrier.

PubMed

Mansfield, Edward D H; de la Rosa, Victor R; Kowalczyk, Radoslaw M; Grillo, Isabelle; Hoogenboom, Richard; Sillence, Katy; Hole, Patrick; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2016-08-16

Functionalised nanomaterials are gaining popularity for use as drug delivery vehicles and, in particular, mucus penetrating nanoparticles may improve drug bioavailability via the oral route. To date, few polymers have been investigated for their muco-penetration, and the effects of systematic structural changes to polymer architectures on the penetration and diffusion of functionalised nanomaterials through mucosal tissue have not been reported. We investigated the influence of poly(2-oxazoline) alkyl side chain length on nanoparticle diffusion; poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), and poly(2-n-propyl-2-oxazoline) were grafted onto the surface of thiolated silica nanoparticles and characterised by FT-IR, Raman and NMR spectroscopy, thermogravimetric analysis, and small angle neutron scattering. Diffusion coefficients were determined in water and in a mucin dispersion (using Nanoparticle Tracking Analysis), and penetration through a mucosal barrier was assessed using an ex vivo fluorescence technique. The addition of a single methylene group in the side chain significantly altered the penetration and diffusion of the materials in both mucin dispersions and mucosal tissue. Nanoparticles functionalised with poly(2-methyl-2-oxazoline) were significantly more diffusive than particles with poly(2-ethyl-2-oxazoline) while particles with poly(2-n-propyl-2-oxazoline) showed no significant increase compared to the unfunctionalised particles. These data show that variations in the polymer structure can radically alter their diffusive properties with clear implications for the future design of mucus penetrating systems.

Stabilizing interactions between aromatic and basic side chains in alpha-helical peptides and proteins. Tyrosine effects on helix circular dichroism.

PubMed

Andrew, Charles D; Bhattacharjee, Samita; Kokkoni, Nicoleta; Hirst, Jonathan D; Jones, Gareth R; Doig, Andrew J

2002-10-30

Here we investigate the structures and energetics of interactions between aromatic (Phe or Tyr) and basic (Lys or Arg) amino acids in alpha-helices. Side chain interaction energies are measured using helical peptides, by quantifying their helicities with circular dichroism at 222 nm and interpreting the results with Lifson-Roig-based helix/coil theory. A difficulty in working with Tyr is that the aromatic ring perturbs the CD spectrum, giving an incorrect helicity. We calculated the effect of Tyr on the CD at 222 nm by deriving the intensities of the bands directly from the electronic and magnetic transition dipole moments through the rotational strengths corresponding to each excited state of the polypeptide. This gives an improved value of the helix preference of Tyr (from 0.48 to 0.35) and a correction to the helicity for the peptides containing Tyr. We find that Phe-Lys, Lys-Phe, Phe-Arg, Arg-Phe, and Tyr-Lys are all stabilizing by -0.10 to -0.18 kcal.mol-1 when placed i, i + 4 on the surface of a helix in aqueous solution, despite the great difference in polarity between these residues. Interactions between these side chains have previously been attributed to cation-pi bonds. A survey of protein structures shows that they are in fact predominantly hydrophobic interactions between the CH2 groups of Lys or Arg and the aromatic rings.

Total Syntheses of (±)-Ovalicin, C4(S*)-Isomer, and Its C5-Analogs and Anti-trypanosomal Activities∥

PubMed Central

Hua, Duy H.; Zhao, Huiping; Battina, Srinivas K.; Lou, Kaiyan; Jimenez, Ana L.; Desper, John; Perchellet, Elisabeth M.; Perchellet, Jean-Pierre H.; Chiang, Peter K.

2008-01-01

Total syntheses of (±)-ovalicin, its C4(S*)-isomer 44, and C5-side chain intermediate 46 were accomplished via an intramolecular Heck reaction of (Z)-3-(t-butyldimethylsilyloxy)-1-iodo-1,6-heptadiene and a catalytic amount of palladium acetate. Subsequent epoxidation, dihydroxylation, methylation and oxidation led to (3S*,5R*,6R*)-5-methoxy-6-(t-butyldimethylsilyloxy)-1-oxaspiro[2.5]octan-4-one (2), a reported intermediate. The addition of a side chain with cis-1-lithio-1,5-dimethyl-1,4-hexadiene (27) followed by oxidation afforded (±)-ovalicin. The functional group manipulation afforded a number of regio- and stereoisomers, which allow the synthesis of analogs for bioevaluation. The structure of 44 was firmly established via a single-crystal X-ray analysis. The stereochemistry at C4 generated from the addition reactions of alkenyllithium with ketones 2, 40, and 45 is dictated by C6-alkoxy functionality. Anti-trypanosomal activities of various ovalicin analogs and synthetic intermediates were evaluated, and C5-side chain analog, 46, shows the strongest activity. Compound 44 shows antiproliferative effect against HL-60 tumor cells in vitro. Compounds 46 and a precursor, (3S*,4R*,5R*,6R*)-5-methoxy-4-[(E)-1’,5’-dimethylhexa-1’,4’–dienyl)]-6-(t-butyldimethylsilyloxy)-1-oxaspiro[2.5]octan-4-ol (28), may be explored for the development of anti-parasitic drugs. PMID:18356059

Interactions between Membranes and "Metaphilic" Polypeptide Architectures with Diverse Side-Chain Populations.

PubMed

Lee, Michelle W; Han, Ming; Bossa, Guilherme Volpe; Snell, Carly; Song, Ziyuan; Tang, Haoyu; Yin, Lichen; Cheng, Jianjun; May, Sylvio; Luijten, Erik; Wong, Gerard C L

2017-03-28

At physiological conditions, most proteins or peptides can fold into relatively stable structures that present on their molecular surfaces specific chemical patterns partially smeared out by thermal fluctuations. These nanoscopically defined patterns of charge, hydrogen bonding, and/or hydrophobicity, along with their elasticity and shape stability (folded proteins have Young's moduli of ∼1 × 10 8 Pa), largely determine and limit the interactions of these molecules, such as molecular recognition and allosteric regulation. In this work, we show that the membrane-permeating activity of antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) can be significantly enhanced using prototypical peptides with "molten" surfaces: metaphilic peptides with quasi-liquid surfaces and adaptable shapes. These metaphilic peptides have a bottlebrush-like architecture consisting of a rigid helical core decorated with mobile side chains that are terminated by cationic or hydrophobic groups. Computer simulations show that these flexible side chains can undergo significant rearrangement in response to different environments, giving rise to adaptable surface chemistry of the peptide. This quality makes it possible to control their hydrophobicity over a broad range while maintaining water solubility, unlike many AMPs and CPPs. Thus, we are able to show how the activity of these peptides is amplified by hydrophobicity and cationic charge, and rationalize these results using a quantitative mean-field theory. Computer simulations show that the shape-changing properties of the peptides and the resultant adaptive presentation of chemistry play a key enabling role in their interactions with membranes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xi, Liang; Bird, Matthew; Mauro, Gina

Triplet excitons created in poly-2,7-(9,9-dihexyl)fluorene (pF) chains with end trap groups in solution are efficiently transported to and captured by the end groups. The triplets explore the entire lengths of the chains, even for ~100 nm long chains enabling determination of the completeness of end capping. The results show that the chains continuous: they may contain transient barriers or traps, such as those from fluctuations of dihedral angles, but are free of major defects that stop motion of the triplets. Quantitative determinations are aided by the addition of a strong electron donor, TMPD, which removes absorption bands of the end-trappedmore » triplets. For chains having at least one end trap, triplet capture is quantitative on the 1 µs timescale imposed by the use of the donor. Fractions of chains having no end traps were 0.15 for pF samples with anthraquinone (AQ) end traps and 0.063 with naphthylimide (NI) end traps. These determinations agreed with measurements by NMR for short (<40 polymer repeat units (PRU)) chains, where NMR determinations are accurate. The results find no evidence for traps or barriers to transport of triplets, and places limits on the possible presence of defects as impenetrable barriers to less than one per 300 PRU. The present results present a paradigm different from the current consensus, derived from observations of singlet excitons, that conjugated chains are divided into “segments,” perhaps by some kind of defects. For the present pF chains, the segmentation either does not apply to triplet excitons or is transient so that the defects are healed or surmounted in times much shorter than 1 µs. Triplets on chains without end trap groups transfer to chains with end traps on a slower time scale. Rate constants for these bimolecular triplet transfer reactions were found to increase with the length of the accepting chain, as did rate constants for triplet transfer to the chains from small molecules like biphenyl. As a result, a second set of polyfluorenes with 2-butyloctyl side chains was found to have a much lower completeness of end capping.« less

Mechanistic insights into phosphoprotein-binding FHA domains.

PubMed

Liang, Xiangyang; Van Doren, Steven R

2008-08-01

[Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family of FHA domains by a bioinformatics approach. The phosphopeptide-dependent dynamics of an FHA domain, SH2 domain, and PTB domain suggest a common theme: rigid, preformed binding surfaces support van der Waals contacts that provide favorable binding enthalpy. Despite the lack of pronounced conformational changes in FHA domains linked to binding events, more subtle adjustments may be possible. In the one FHA domain tested, phosphothreonine peptide binding is accompanied by increased flexibility just outside the binding site and increased rigidity across the beta-sandwich. The folding of the same FHA domain progresses through near-native intermediates that stabilize the recognition loops in the center of the phosphoprotein-binding surface; this may promote rigidity in the interface and affinity for targets phosphorylated on threonine.

Binding of tetramethylammonium to polyether side-chained aromatic hosts. Evaluation of the binding contribution from ether oxygen donors.

PubMed

Bartoli, Sandra; De Nicola, Gina; Roelens, Stefano

2003-10-17

A set of macrocyclic and open-chain aromatic ligands endowed with polyether side chains has been prepared to assess the contribution of ether oxygen donors to the binding of tetramethylammonium (TMA), a cation believed incapable of interacting with oxygen donors. The open-chain hosts consisted of an aromatic binding site and side chains possessing a variable number of ether oxygen donors; the macrocyclic ligands were based on the structure of a previously investigated host, the dimeric cyclophane 1,4-xylylene-1,4-phenylene diacetate (DXPDA), implemented with polyether-type side chains in the backbone. Association to tetramethylammonium picrate (TMAP) was measured in CDCl(3) at T = 296 K by (1)H NMR titrations. Results confirm that the main contribution to the binding of TMA comes from the cation-pi interaction established with the aromatic binding sites, but they unequivocally show that polyether chains participate with cooperative contributions, although of markedly smaller entity. Water is also bound, but the two guests interact with aromatic rings and oxygen donors in an essentially noncompetitive way. An improved procedure for the preparation of cyclophanic tetraester derivatives has been developed that conveniently recycles the oligomeric ester byproducts formed in the one-pot cyclization reaction. An alternative entry to benzylic diketones has also been provided that makes use of a low-order cyanocuprate reagent to prepare in fair yields a class of compounds otherwise uneasily accessible.

Synthesis and redox activity of "clicked" triazolylbiferrocenyl polymers, network encapsulation of gold and silver nanoparticles and anion sensing.

PubMed

Rapakousiou, Amalia; Deraedt, Christophe; Irigoyen, Joseba; Wang, Yanlan; Pinaud, Noël; Salmon, Lionel; Ruiz, Jaime; Moya, Sergio; Astruc, Didier

2015-03-02

The design of redox-robust polymers is called for in view of interactions with nanoparticles and surfaces toward applications in nanonetwork design, sensing, and catalysis. Redox-robust triazolylbiferrocenyl (trzBiFc) polymers have been synthesized with the organometallic group in the side chain by ring-opening metathesis polymerization using Grubbs-III catalyst or radical polymerization and with the organometallic group in the main chain by Cu(I) azide alkyne cycloaddition (CuAAC) catalyzed by [Cu(I)(hexabenzyltren)]Br. Oxidation of the trzBiFc polymers with ferricenium hexafluorophosphate yields the stable 35-electron class-II mixed-valent biferrocenium polymer. Oxidation of these polymers with Au(III) or Ag(I) gives nanosnake-shaped networks (observed by transmission electron microscopy and atomic force microscopy) of this mixed-valent Fe(II)Fe(III) polymer with encapsulated metal nanoparticles (NPs) when the organoiron group is located on the side chain. The factors that are suggested to be synergistically responsible for the NP stabilization and network formation are the polymer bulk, the trz coordination, the nearby cationic charge of trzBiFc, and the inter-BiFc distance. For instance, reduction of such an oxidized trzBiFc-AuNP polymer to the neutral trzBiFc-AuNP polymer with NaBH4 destroys the network, and the product flocculates. The polymers easily provide modified electrodes that sense, via the oxidized Fe(II)Fe(III) and Fe(III)Fe(III) polymer states, respectively, ATP(2-) via the outer ferrocenyl units of the polymer and Pd(II) via the inner Fc units; this recognition works well in dichloromethane, but also to a lesser extent in water with NaCl as the electrolyte.

A comparative evaluation of rate of space closure after extraction using E-chain and stretched modules in bimaxillary dentoalveolar protrusion cases.

PubMed

Mitra, Rajat; Londhe, S M; Kumar, Prasanna

2011-04-01

Aim of this study was to compare the rate of space closure between E-chain mechanics in one side of upper arch and by elastomeric module with ligature wire on the contralateral side in same patient. Thirty bimaxillary dentoalveolar protrusion cases were taken up for comprehensive fixed orthodontic treatment after extraction of all first premolars to retract both upper and lower anterior teeth. After initial alignment and levelling, alginate impressions were made for upper and lower arches and models constructed. In the upper arch model a vernier caliper was used to measure the extraction space in both sides from middle point of distal surface of canine to the middle most point of mesial surface of second premolar. This is the amount of space present before the onset of retraction mechanics. During space closure procedure two different retracting components were applied in right and left sides of each case. On right side elastic chain (E-chain) applied in both upper and lower arches and on left side elastomeric module with steel ligature (0.010") stretched double its diameter fixed in both arches. Both the mechanisms produced approximately 250-300 g of force as measured by a tension gauge. After onset of retraction mechanism all patients were recalled after every six weeks for three visits. In all these three visits modules and E-chains were changed. In all three visits impression was made, models constructed, and the remaining available space was measured by a vernier caliper up to 0.1 mm level variations. Mean value for total space closure in case of E-chain was 2.777 mm whereas in case of module with ligature wire the value increased to 3.017 mm. Mean value for rate of space closure in case of E-chain was 0.2143 mm, whereas in case of module with ligature wire the value increased to 0.2343 mm with a standard deviation of 0.001104 and 0.001194, respectively. The standard deviation for total space closure was 0.1305 for E-chain and 0.1487 for module with ligature wire. Space closure by elastomeric module with ligature wire is better than the E-chain.

High-Temperature Shape Memory Behavior of Semicrystalline Polyamide Thermosets.

PubMed

Li, Ming; Guan, Qingbao; Dingemans, Theo J

2018-05-21

We have explored semicrystalline poly(decamethylene terephthalamide) (PA 10T) based thermosets as single-component high-temperature (>200 °C) shape memory polymers (SMPs). The PA 10T thermosets were prepared from reactive thermoplastic precursors. Reactive phenylethynyl (PE) functionalities were either attached at the chain termini or placed as side groups along the polymer main chain. The shape fixation and recovery performance of the thermoset films were investigated using a rheometer in torsion mode. By controlling the M n of the reactive oligomers, or the PE concentration of the PE side-group functionalized copolyamides, we were able to design dual-shape memory PA 10T thermosets with a broad recovery temperature range of 227-285 °C. The thermosets based on the 1000 g mol -1 reactive PE precursor and the copolyamide with 15 mol % PE side groups show the highest fixation rate (99%) and recovery rate (≥90%). High temperature triple-shape memory behavior can be achieved as well when we use the melt transition ( T m ≥ 200 °C) and the glass transition ( T g = ∼125 °C) as the two switches. The recovery rate of the two recovery steps are highly dependent on the crystallinity of the thermosets and vary within a wide range of 74%-139% and 40-82% for the two steps, respectively. Reversible shape memory events could also be demonstrated when we perform a forward and backward deformation in a triple shape memory cycle. We also studied the angular recovery velocity as a function of temperature, which provides a thermokinematic picture of the shape recovery process and helps to program for desired shape memory behavior.

High-Temperature Shape Memory Behavior of Semicrystalline Polyamide Thermosets

PubMed Central

2018-01-01

We have explored semicrystalline poly(decamethylene terephthalamide) (PA 10T) based thermosets as single-component high-temperature (>200 °C) shape memory polymers (SMPs). The PA 10T thermosets were prepared from reactive thermoplastic precursors. Reactive phenylethynyl (PE) functionalities were either attached at the chain termini or placed as side groups along the polymer main chain. The shape fixation and recovery performance of the thermoset films were investigated using a rheometer in torsion mode. By controlling the Mn of the reactive oligomers, or the PE concentration of the PE side-group functionalized copolyamides, we were able to design dual-shape memory PA 10T thermosets with a broad recovery temperature range of 227–285 °C. The thermosets based on the 1000 g mol–1 reactive PE precursor and the copolyamide with 15 mol % PE side groups show the highest fixation rate (99%) and recovery rate (≥90%). High temperature triple-shape memory behavior can be achieved as well when we use the melt transition (Tm ≥ 200 °C) and the glass transition (Tg = ∼125 °C) as the two switches. The recovery rate of the two recovery steps are highly dependent on the crystallinity of the thermosets and vary within a wide range of 74%–139% and 40–82% for the two steps, respectively. Reversible shape memory events could also be demonstrated when we perform a forward and backward deformation in a triple shape memory cycle. We also studied the angular recovery velocity as a function of temperature, which provides a thermokinematic picture of the shape recovery process and helps to program for desired shape memory behavior. PMID:29742899

Peptide adsorption on the hydrophobic surface: A free energy perspective

NASA Astrophysics Data System (ADS)

Sheng, Yuebiao; Wang, Wei; Chen, P.

2011-05-01

Protein adsorption is a very attractive topic which relates to many novel applications in biomaterials, biotechnology and nanotechnology. Ionic complementary peptides are a group of novel nano-biomaterials with many biomedical applications. In this work, molecular dynamics simulations of the ionic-complementary peptide EAK16-II on a hydrophobic graphite surface were performed under neutral, acidic and basic solution conditions. Adsorption free energy contour maps were obtained by analyzing the dynamical trajectories. Hydrophobic interactions were found to govern the adsorption of the first peptide molecule, and both hydrophobic and electrostatic interactions contributed to the adsorption of the second peptide molecule. Especially under acidic and basic solution conditions, interplay existed among chain-chain hydrophobic, chain-surface hydrophobic and chain-chain electrostatic interactions during the adsorption of the second peptide molecule. Non-charged residues were found to lie on the graphite surface, while charged residue side-chains oriented towards the solution after the peptide deposited on the surface. These results provide a basis for understanding peptide adsorption on the hydrophobic surface under different solution conditions, which is useful for novel applications such as bioactive implant devices and drug delivery material design.

Fine-tuning blend morphology via alkylthio side chain engineering towards high performance non-fullerene polymer solar cells

NASA Astrophysics Data System (ADS)

Li, Ling; Feng, Liuliu; Yuan, Jun; Peng, Hongjian; Zou, Yingping; Li, Yongfang

2018-03-01

Two medium bandgap polymers (ffQx-TS1, ffQx-TS2) were designed and synthesized to investigate the influence of different alkylthio side chain on the morphology and photovoltaic performance of non-fullerene polymer solar cells (PSCs). Both polymers exhibit similar molecular weights and comparable the highest occupied molecular orbital (HOMO) energy level. However, the polymer with straight alkylthio chain delivers a root-mean-square (RMS) of 0.86 nm, which is slightly lower than that with branched chain (1.40 nm). The lower RMS benefits the ohmic contact between the active lay and interface layer, thus enhanced short circuit current (Jsc) (from 13.54 mA cm-1 to 15.25 mA cm-1) could be obtained. Due to the enhancement of Jsc, better power conversion efficiency (PCE) of 7.69% for ffQx-TS2 could be realized. These results indicated that alkylthio side chain engineering is a promising method to improve photovoltaic performance.

The effects of side-chain-induced disorder on the emission spectra and quantum yields of oligothiophene nano-aggregates. A combined experimental and MD-TDDFT study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Jiyun; Jeon, SuKyung; Kim, Janice J.

2014-07-24

Oligomeric thiophenes are commonly-used components in organic electronics and solar cells. These molecules stack and/or aggregate readily under the processing conditions used to form thin films for these applications, significantly altering their optical and charge-transport properties. To determine how these effects depend on the substitution pattern of the thiophene main chains, nano-aggregates of three sexi-thiophene (6T) oligomers having different alkyl substitution patterns were formed using solvent poisoning techniques and studied using steady-state and time-resolved emission spectroscopy. The results indicate the substantial role played by the side-chain substituents in determining the emissive properties of these species. Both the measured spectral changesmore » and their dependence on substitution are well modeled by combined quantum chemistry and molecular dynamics simulations. The simulations connect the side-chain-induced disorder, which determines the favorable chain packing configurations within the aggregates, with their measured electronic spectra.« less

Solution-processable ambipolar diketopyrrolopyrrole-selenophene polymer with unprecedentedly high hole and electron mobilities.

PubMed

Lee, Junghoon; Han, A-Reum; Kim, Jonggi; Kim, Yiho; Oh, Joon Hak; Yang, Changduk

2012-12-26

There is a fast-growing demand for polymer-based ambipolar thin-film transistors (TFTs), in which both n-type and p-type transistor operations are realized in a single layer, while maintaining simplicity in processing. Research progress toward this end is essentially fueled by molecular engineering of the conjugated backbones of the polymers and the development of process architectures for device fabrication, which has recently led to hole and electron mobilities of more than 1.0 cm(2) V(-1) s(-1). However, ambipolar polymers with even higher performance are still required. By taking into account both the conjugated backbone and side chains of the polymer component, we have developed a dithienyl-diketopyrrolopyrrole (TDPP) and selenophene containing polymer with hybrid siloxane-solubilizing groups (PTDPPSe-Si). A synergistic combination of rational polymer backbone design, side-chain dynamics, and solution processing affords an enormous boost in ambipolar TFT performance, resulting in unprecedentedly high hole and electron mobilities of 3.97 and 2.20 cm(2) V(-1) s(-1), respectively.

Biotin-Functionalized Semiconducting Polymer in an Organic Field Effect Transistor and Application as a Biosensor

PubMed Central

Kim, Zin-Sig; Lim, Sang Chul; Kim, Seong Hyun; Yang, Yong Suk; Hwang, Do-Hoon

2012-01-01

This report presents biotin-functionalized semiconducting polymers that are based on fluorene and bithiophene co-polymers (F8T2). Also presented is the application of these polymers to an organic thin film transistor used as a biosensor. The side chains of fluorene were partially biotinylated after the esterification of the biotin with corresponding alcohol-groups at the side chain in F8T2. Their properties as an organic semiconductor were tested using an organic thin film transistor (OTFT) and were found to show typical p-type semiconductor curves. The functionality of this biosensor in the sensing of biologically active molecules such as avidin in comparison with bovine serum albumin (BSA) was established through a selective decrease in the conductivity of the transistor, as measured with a device that was developed by the authors. Changes to the optical properties of this polymer were also measured through the change in the color of the UV-fluorescence before and after a reaction with avidin or BSA. PMID:23112654

Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Barrientos-Salcedo, Carolina; Campos-Fernández, Linda; Alvarado-Salazar, Andres; Esquivel, Rodolfo O.

2015-08-01

Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys-Asn-Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

DFT conformational studies of the HI-6 molecule

NASA Astrophysics Data System (ADS)

Silva, Gustavo R.; Borges, Itamar; Figueroa-Villar, Jose D.

A systematic study of the oxime HI-6 [1-(2-hydroxyiminomethyl-1-pyridinium)-1-(4-carboxy-aminopyridinium)dimethyl ether] hydrochloride, which is one of the most promising antidotes against soman intoxication, was carried out using density functional theory with the B3LYP (Becke, Lee, Yang, and Parr) method and the 6-31+G*, 6-31+G*, and 6-31+G** basis sets. Rotational barriers, equilibrium geometries, and charge distributions were calculated in order to investigate the role of the side chain for the larger oximes used as antidotes in the treatment of neurotoxic organophosphate poisoning. Also reported is the comparison between HI-6 and pralidoxime (2-PAM), a smaller oxime previously studied in our research group. It is shown that conformation minima for the protonated E isomer do not depend on the size of the side chain; on the other hand, this effect has a pronounced influence on the protonated Z isomer. For the unprotonated isomers, other effects, such as electrostatic interactions and resonance, should be taken into account in their conformational analysis.

Radiolysis of N-acetyl amino acids as model compounds for radiation degradation of polypeptides

NASA Astrophysics Data System (ADS)

Wayne Garrett, R.; Hill, David J. T.; Ho, Sook-Ying; O'Donnell, James H.; O'Sullivan, Paul W.; Pomery, Peter J.

Radiation chemical yields of (i) the volatile radiolysis products and (ii) the trapped free radicals from the y-radiolysis of the N-acetyl derivatives of glycine, L-valine, L-phenylalanine and L-tyrosine in the polycrystalline state have been determined at room temperature (303 K). Carbon dioxide was found to be the major molecular product for all these compounds with G(CO 2) varying from 0.36 for N-acetyl-L-tyrosine to 8 for N-acetyl-L-valine. There was evidence for some scission of the N-C α bond, indicated by the production of acetamide and the corresponding aliphatic acid, but the determination reaction was found to be of much lesser importance than the decarboxylation reaction. A protective effect of the aromatic ring in N-acetyl-L-phenylalanine and in N-acetyl-L-tyrosine was indicated by the lower yields of volatile products for these compounds. The yields of trapped free radicals were found to vary with the nature of the amino acid side chain, increasing with chain length and chain branching. The radical yields were decreased by incorporation of an aromatic moiety in the side chain, this effect being greater for the tyrosyl side chain than for the phenyl side chain. The G(R·) values showed a good correlation with G(CO 2) indicating that a common reaction may be involved in radical production and carbon dioxide formation.

Diterpene lactones with labdane, halimane and clerodane frameworks.

PubMed

Silva, Lúcia; Gomes, Arlindo C; Rodilla, Jesus M L

2011-04-01

The labdane, halimane and clerodane type diterpenoids are compounds that have been isolated in plants of several families. These molecules and their derivatives with a lactone group on the side chain or on the decaline system, have a great interest because of their biological properties as insect antifeedant, antiviral, cytotoxic and trypanocidal. The scope of this review is lactones diterpenoids with labdane, halimane and clerodane frameworks.

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2013-10-01

acids. These sites constitute a variable environment, with the effect of mutations largely isolated to effects on interactions with the P4 side chain. 2...desires to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only...first five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2012-10-14

effect of mutations largely isolated to effects on interactions with the P4 side chain. 2) Most mutations at some sites (e.g. 126, 128) decrease...to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only ground...five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus of the

Dynamic contact angle cycling homogenizes heterogeneous surfaces.

PubMed

Belibel, R; Barbaud, C; Mora, L

2016-12-01

In order to reduce restenosis, the necessity to develop the appropriate coating material of metallic stent is a challenge for biomedicine and scientific research over the past decade. Therefore, biodegradable copolymers of poly((R,S)-3,3 dimethylmalic acid) (PDMMLA) were prepared in order to develop a new coating exhibiting different custom groups in its side chain and being able to carry a drug. This material will be in direct contact with cells and blood. It consists of carboxylic acid and hexylic groups used for hydrophilic and hydrophobic character, respectively. The study of this material wettability and dynamic surface properties is of importance due to the influence of the chemistry and the potential motility of these chemical groups on cell adhesion and polymer kinetic hydrolysis. Cassie theory was used for the theoretical correction of contact angles of these chemical heterogeneous surfaces coatings. Dynamic Surface Analysis was used as practical homogenizer of chemical heterogeneous surfaces by cycling during many cycles in water. In this work, we confirmed that, unlike receding contact angle, advancing contact angle is influenced by the difference of only 10% of acidic groups (%A) in side-chain of polymers. It linearly decreases with increasing acidity percentage. Hysteresis (H) is also a sensitive parameter which is discussed in this paper. Finally, we conclude that cycling provides real information, thus avoiding theoretical Cassie correction. H(10)is the most sensible parameter to %A. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

PubMed

Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

2016-10-01

A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Liquid chromatography fractionation with gas chromatography/mass spectrometry and preparative gas chromatography-nuclear magnetic resonance analysis of selected nonylphenol polyethoxylates.

PubMed

Wu, Ze-ying; Rühle, Christian P G; Marriott, Philip J

2011-07-01

Commercial nonylphenol polyethoxylates, designated as NPnEOs, where n is the number of ethoxy groups, comprise a range of ethoxylate groups. According to the starting material nonylphenol, they may also be composed of a complex mix of isomeric nonyl substituents. In order to study more fully the heterogeneity arising from both the ethoxylate and nonyl groups, a mixture of NPnEOs is first fractionated by normal phase liquid chromatography (NPLC) into separate fractions comprising individual ethoxymers, n. Preparative collection of each early elution ethoxymer fraction allows further separation of different isomeric nonyl group components by using analytical gas chromatography/mass spectrometry (GC/MS). The nonyl isomers are not resolved in the NPLC method. The distribution of the isomeric nonyl side chain of different ethoxymers bears close resemblance with each other, and also with the original nonylphenol starting material, although separation efficiency of the nonyl isomers for each ethoxymer decreases with increasing ethoxymer number. Mass spectrometry of the separated isomers display close similarity for presumed equivalent isomers in each fraction, based on elution order of the nonyl isomers. This suggests that each corresponding peak has the same isomer structure. Mass spectra are interpreted based on branching within the nonyl side chain. Preparative GC coupled with MS and nuclear magnetic resonance spectroscopy elucidated the molecular structure of one of the resolved isomers as 4-(1,3-dimethyl-1-propyl-butyl)-phenol diethoxylate. Copyright © 2011 Elsevier B.V. All rights reserved.

Conceptually new deltanoids (vitamin D analogs) inhibit multistage skin tumorigenesis.

PubMed

Kensler, T W; Dolan, P M; Gange, S J; Lee, J K; Wang, Q; Posner, G H

2000-07-01

Development of vitamin D analogs (deltanoids) as chemopreventive agents requires separation of desirable antiproliferative and pro-differentiating activities from the undesirable calcemic activity also found in the hormone calcitriol (1 alpha, 25-dihydroxyvitamin D(3)). Therefore, several conceptually new deltanoids were synthesized with modifications to the 1alpha- and/or 25-hydroxyl groups, positions traditionally considered essential for stimulating biological responses. In this study, 1 beta-hydroxymethyl-3-epi-25-hydroxyvitamin D(3), a non-calcemic CH(2) homolog of the natural hormone with antiproliferative activity in vitro, was ineffective as an inhibitor of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced induction of ornithine decarboxylase activity in mouse epidermis. However, a hybrid analog incorporating not only the calcemia-ablating 1 beta-hydroxymethyl alteration, but potentiating C,D ring 16-unsaturation and side chain 24,24-fluorination and 26, 27-homologation was found to be as effective as calcitriol. Several non-calcemic 24- or 25-t-butyl sulfones, some containing side chain fluorination but all lacking the 25-hydroxyl group, were also shown to be active in this assay. Three sulfones and the 1 beta-hydroxymethyl hybrid were evaluated as inhibitors of multistage carcinogenesis in mouse skin. Female CD-1 mice were initiated with a single dose of 7,12-dimethylbenz[a]anthracene and then promoted twice weekly for 20 weeks with TPA. Deltanoids were applied topically 30 min before TPA. Unlike calcitriol, none of the atypical deltanoids affected body weight gain in these animals. Minimal effects on urinary calcium excretion were observed following chronic treatment with these analogs. All deltanoids inhibited the incidence and multiplicity of papilloma formation, with the hybrid analog showing the greatest efficacy. With this deltanoid, tumor incidence was significantly reduced by 28% and tumor multiplicity by 63%. These results, coupled with the rich chemical diversity available in side chain sulfur-containing deltanoids, particularly when combined with A ring modifications such as 1 beta-hydroxylalkyl groups, provide important new advances in the fundamental understanding of chemical structure-biological activity relationships as well as more potent and safe vitamin D analogs for cancer chemoprevention and other medicinal uses.

BetaSCPWeb: side-chain prediction for protein structures using Voronoi diagrams and geometry prioritization.

PubMed

Ryu, Joonghyun; Lee, Mokwon; Cha, Jehyun; Laskowski, Roman A; Ryu, Seong Eon; Kim, Deok-Soo

2016-07-08

Many applications, such as protein design, homology modeling, flexible docking, etc. require the prediction of a protein's optimal side-chain conformations from just its amino acid sequence and backbone structure. Side-chain prediction (SCP) is an NP-hard energy minimization problem. Here, we present BetaSCPWeb which efficiently computes a conformation close to optimal using a geometry-prioritization method based on the Voronoi diagram of spherical atoms. Its outputs are visual, textual and PDB file format. The web server is free and open to all users at http://voronoi.hanyang.ac.kr/betascpweb with no login requirement. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fuel cell catalyst layers containing short-side-chain perfluorosulfonic acid ionomers

NASA Astrophysics Data System (ADS)

Peron, Jennifer; Edwards, Dave; Haldane, Mark; Luo, Xiaoyan; Zhang, Yongming; Holdcroft, Steven; Shi, Zhiqing

Porous catalyst layers (CLs) containing short-side-chain (SSC) perfluorosulfonic acid (PFSA) ionomers of different ion exchange capacity (IEC: 1.3, 1.4 and 1.5 meq g -1) were deposited onto Nafion 211 to form catalyst-coated membranes. The porosity of SSC-PFSA-based CLs is larger than Nafion-CL analogues. CLs incorporating SSC ionomer extend the current density of fuel cell polarization curves at elevated temperature and lower relative humidity compared to those based on long-side chain PFSA (e.g., Nafion)-based CLs. Fuel cell polarization performance was greatly improved at 110 °C and 30% relative humidity (RH) when SSC PFSI was incorporated into the catalyst layer.

Interaction of silicene with amino acid analogues—from physical to chemical adsorption in gas and solvated phases

NASA Astrophysics Data System (ADS)

Jagvaral, Yesukhei; He, Haiying; Pandey, Ravindra

2018-01-01

Silicene is an emerging 2D material, and an understanding of its interaction with amino acids, the basic building blocks of protein, is of fundamental importance. In this paper, we investigate the nature of adsorption of amino-acid analogues on silicene employing density functional theory and an implicit solvation model. Amino acid analogues are defined as CH3-R molecules, where R is the functional group of the amino acid side chain. The calculated results find three distinct groups within the amino-acid analogues considered: (i) group I, which includes MeCH3 and MeSH, interacts with silicene via the van der Waals dispersive terms leading to physisorbed configurations; (ii) group II strongly interacts with silicene forming Si-O/N chemical bonds in the chemisorbed configurations; and (iii) group III, which consists of the phenyl group, interacts with silicene via π-π interactions leading to physisorbed configurations. The results show that the lateral chains of the amino acids intrinsically determine the interactions between protein and silicene at the interface under the given physiological conditions.

Highly Sensitive Thin-Film Field-Effect Transistor Sensor for Ammonia with the DPP-Bithiophene Conjugated Polymer Entailing Thermally Cleavable tert-Butoxy Groups in the Side Chains.

PubMed

Yang, Yang; Zhang, Guanxin; Luo, Hewei; Yao, Jingjing; Liu, Zitong; Zhang, Deqing

2016-02-17

The sensing and detection of ammonia have received increasing attention in recent years because of the growing emphasis on environmental and health issues. In this paper, we report a thin-film field-effect transistor (FET)-based sensor for ammonia and other amines with remarkable high sensitivity and satisfactory selectivity by employing the DPP-bithiophene conjugated polymer pDPPBu-BT in which tert-butoxycarboxyl groups are incorporated in the side chains. This polymer thin film shows p-type semiconducting property. On the basis of TGA and FT-IR analysis, tert-butoxycarboxyl groups can be transformed into the -COOH ones by eliminating gaseous isobutylene after thermal annealing of pDPPBu-BT thin film at 240 °C. The FET with the thermally treated thin film of pDPPBu-BT displays remarkably sensitive and selective response toward ammonia and volatile amines. This can be attributed to the fact that the elimination of gaseous isobutylene accompanies the formation of nanopores with the thin film, which will facilitate the diffusion and interaction of ammonia and other amines with the semiconducting layer, leading to high sensitivity and fast response for this FET sensor. This FET sensor can detect ammonia down to 10 ppb and the interferences from other volatile analytes except amines can be negligible.

Quantum Computational Calculations of the Ionization Energies of Acidic and Basic Amino Acids: Aspartate, Glutamate, Arginine, Lysine, and Histidine

NASA Astrophysics Data System (ADS)

de Guzman, C. P.; Andrianarijaona, M.; Lee, Y. S.; Andrianarijaona, V.

An extensive knowledge of the ionization energies of amino acids can provide vital information on protein sequencing, structure, and function. Acidic and basic amino acids are unique because they have three ionizable groups: the C-terminus, the N-terminus, and the side chain. The effects of multiple ionizable groups can be seen in how Aspartate's ionizable side chain heavily influences its preferred conformation (J Phys Chem A. 2011 April 7; 115(13): 2900-2912). Theoretical and experimental data on the ionization energies of many of these molecules is sparse. Considering each atom of the amino acid as a potential departing site for the electron gives insight on how the three ionizable groups affect the ionization process of the molecule and the dynamic coupling between the vibrational modes. In the following study, we optimized the structure of each acidic and basic amino acid then exported the three dimensional coordinates of the amino acids. We used ORCA to calculate single point energies for a region near the optimized coordinates and systematically went through the x, y, and z coordinates of each atom in the neutral and ionized forms of the amino acid. With the calculations, we were able to graph energy potential curves to better understand the quantum dynamic properties of the amino acids. The authors thank Pacific Union College Student Association for providing funds.

A Vibrational Spectral Maker for Probing the Hydrogen-Bonding Status of Protonated Asp and Glu Residues

PubMed Central

Nie, Beining; Stutzman, Jerrod; Xie, Aihua

2005-01-01

Hydrogen bonding is a fundamental element in protein structure and function. Breaking a single hydrogen bond may impair the stability of a protein. We report an infrared vibrational spectral marker for probing the hydrogen-bond number for buried, protonated Asp or Glu residues in proteins. Ab initio computational studies were performed on hydrogen-bonding interactions of a COOH group with a variety of side-chain model compounds of polar and charged amino acids in vacuum using density function theory. For hydrogen-bonding interactions with polar side-chain groups, our results show a strong correlation between the C=O stretching frequency and the hydrogen bond number of a COOH group: ∼1759–1776 cm−1 for zero, ∼1733–1749 cm−1 for one, and 1703–1710 cm−1 for two hydrogen bonds. Experimental evidence for this correlation will be discussed. In addition, we show an approximate linear correlation between the C=O stretching frequency and the hydrogen-bond strength. We propose that a two-dimensional infrared spectroscopy, C=O stretching versus O-H stretching, may be employed to identify the specific type of hydrogen-bonding interaction. This vibrational spectral marker for hydrogen-bonding interaction is expected to enhance the power of time-resolved Fourier transform infrared spectroscopy for structural characterization of functionally important intermediates of proteins. PMID:15653739

Raspberry Ketone Analogs: Vapour Pressure Measurements and Attractiveness to Queensland Fruit Fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae)

PubMed Central

Hanssen, Benjamin L.; Jamie, Joanne F.; Jamie, Ian M.; Siderhurst, Matthew S.; Taylor, Phillip W.

2016-01-01

The Queensland fruit fly, Bactrocera tryoni (Froggatt) (Q-fly), is a major horticultural pest in Eastern Australia. Effective monitoring, male annihilation technique (MAT) and mass trapping (MT) are all important for control and require strong lures to attract flies to traps or toxicants. Lure strength is thought to be related in part to volatility, but little vapour pressure data are available for most Q-fly lures. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) and analogs that had esters (acetyl, difluoroacetyl, trifluoroacetyl, formyl, propionyl) and ethers (methyl ether, trimethylsilyl ether) in replacement of the phenolic group, and in one case also had modification of the 2-butanone side chain, were measured for their vapour pressures by differential scanning calorimetry (DSC), and their attractiveness to Q-fly was assessed in small cage environmentally controlled laboratory bioassays. Maximum response of one category of compounds, containing both 2-butanone side chain and ester group was found to be higher than that of the other group of compounds, of which either of 2-butanone or ester functionality was modified. However, linear relationship between vapour pressure and maximum response was not significant. The results of this study indicate that, while volatility may be a factor in lure effectiveness, molecular structure is the dominating factor for the series of molecules investigated. PMID:27196605

Efficient synthesis of anacardic acid analogues and their antibacterial activities.

PubMed

Mamidyala, Sreeman K; Ramu, Soumya; Huang, Johnny X; Robertson, Avril A B; Cooper, Matthew A

2013-03-15

Anacardic acid derivatives exhibit a broad range of biological activities. In this report, an efficient method for the synthesis of anacardic acid derivatives was explored, and a small set of salicylic acid variants synthesised retaining a constant hydrophobic element (a naphthyl tail). The naphthyl side chain was introduced via Wittig reaction and the aldehyde installed using directed ortho-metalation reaction of the substituted o-anisic acids. The failure of ortho-metalation using unprotected carboxylic acid group compelled us to use directed ortho-metalation in which a tertiary amide was used as a strong ortho-directing group. In the initial route, tertiary amide cleavage during final step was challenging, but cleaving the tertiary amide before Wittig reaction was beneficial. The Wittig reaction with protected carboxylic group (methyl ester) resulted in side-products whereas using sodium salt resulted in higher yields. The novel compounds were screened for antibacterial activity and cytotoxicity. Although substitution on the salicylic head group enhanced antibacterial activities they also enhanced cytotoxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mistletoe lectin I in complex with galactose and lactose reveals distinct sugar-binding properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mikeska, Ruth; Wacker, Roland; Arni, Raghuvir

2005-01-01

The structures of mistletoe lectin I in complex with lactose and galactose reveal differences in binding by the two known sites in subdomains α1 and γ2 and suggest the presence of a third low-affinity site in subdomain β1. The structures of mistletoe lectin I (ML-I) from Viscum album complexed with lactose and galactose have been determined at 2.3 Å resolution and refined to R factors of 20.9% (R{sub free} = 23.6%) and 20.9 (R{sub free} = 24.6%), respectively. ML-I is a heterodimer and belongs to the class of ribosome-inactivating proteins of type II, which consist of two chains. The A-chainmore » has rRNA N-glycosidase activity and irreversibly inhibits eukaryotic ribosomes. The B-chain is a lectin and preferentially binds to galactose-terminated glycolipids and glycoproteins on cell membranes. Saccharide binding is performed by two binding sites in subdomains α1 and γ2 of the ML-I B-chain separated by ∼62 Å from each other. The favoured binding of galactose in subdomain α1 is achieved via hydrogen bonds connecting the 4-hydroxyl and 3-hydroxyl groups of the sugar moiety with the side chains of Asp23B, Gln36B and Lys41B and the main chain of 26B. The aromatic ring of Trp38B on top of the preferred binding pocket supports van der Waals packing of the apolar face of galactose and stabilizes the sugar–lectin complex. In the galactose-binding site II of subdomain γ2, Tyr249B provides the hydrophobic stacking and the side chains of Asp235B, Gln238B and Asn256B are hydrogen-bonding partners for galactose. In the case of the galactose-binding site I, the 2-hydroxyl group also stabilizes the sugar–protein complex, an interaction thus far rarely detected in galactose-specific lectins. Finally, a potential third low-affinity galactose-binding site in subunit β1 was identified in the present ML-I structures, in which a glycerol molecule from the cryoprotectant buffer has bound, mimicking the sugar compound.« less

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, Pengjie; Wang, Huan; Mo, Daize

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

DOE PAGES

Chao, Pengjie; Wang, Huan; Mo, Daize; ...

2017-12-18

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

Correction of erroneously packed protein's side chains in the NMR structure based on ab initio chemical shift calculations.

PubMed

Zhu, Tong; Zhang, John Z H; He, Xiao

2014-09-14

In this work, protein side chain (1)H chemical shifts are used as probes to detect and correct side-chain packing errors in protein's NMR structures through structural refinement. By applying the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of chemical shifts, incorrect side chain packing was detected in the NMR structures of the Pin1 WW domain. The NMR structure is then refined by using molecular dynamics simulation and the polarized protein-specific charge (PPC) model. The computationally refined structure of the Pin1 WW domain is in excellent agreement with the corresponding X-ray structure. In particular, the use of the PPC model yields a more accurate structure than that using the standard (nonpolarizable) force field. For comparison, some of the widely used empirical models for chemical shift calculations are unable to correctly describe the relationship between the particular proton chemical shift and protein structures. The AF-QM/MM method can be used as a powerful tool for protein NMR structure validation and structural flaw detection.

Entropy and enthalpy of interaction between amino acid side chains in nanopores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaitheeswaran, S., E-mail: vaithee05@gmail.com; Thirumalai, D.; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742

2014-12-14

Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientationsmore » between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.« less

Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure.

PubMed

Schumann, Marcel; Armen, Roger S

2013-05-30

Molecular docking of small-molecules is an important procedure for computer-aided drug design. Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding. However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem. Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers. We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0.693 vs. 0.623). Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures. Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement. Copyright © 2013 Wiley Periodicals, Inc.

Contributions of all 20 amino acids at site 96 to the stability and structure of T4 lysozyme

PubMed Central

Mooers, Blaine H M; Baase, Walter A; Wray, Jonathan W; Matthews, Brian W

2009-01-01

To try to resolve the loss of stability in the temperature-sensitive mutant of T4 lysozyme, Arg 96 → His, all of the remaining 18 naturally occurring amino acids were substituted at site 96. Also, in response to suggestions that the charged residues Lys85 and Asp89, which are 5–8 Å away, may have important effects, each of these amino acids was replaced with alanine. Crystal structures were determined for many of the variants. With the exception of the tryptophan and valine mutants R96W and R96V, the crystallographic analysis shows that the substituted side chain following the path of Arg96 in wildtype (WT). The melting temperatures of the variants decrease by up to ∼16°C with WT being most stable. There are two site 96 replacements, with lysine or glutamine, that leave the stability close to that of WT. The only element that the side chains of these residues have in common with the WT arginine is the set of three carbon atoms at the Cα, Cβ, and Cγ positions. Although each side chain is long and flexible with a polar group at the distal position, the details of the hydrogen bonding to the rest of the protein differ in each case. Also, the glutamine replacement lacks a positive charge. This shows that there is some adaptability in achieving full stabilization at this site. At the other extreme, to be maximally destabilizing a mutation at site 96 must not only eliminate favorable interactions but also introduce an unfavorable element such as steric strain or a hydrogen-bonding group that remains unsatisfied. Overall, the study highlights the essential need for atomic resolution site-specific structural information to understand and to predict the stability of mutant proteins. It can be very misleading to simply assume that conservative amino acid substitutions cause small changes in stability, whereas large stability changes are associated with nonconservative replacements. PMID:19384988

Odd-even effect on the formation of aqueous biphasic systems formed by 1-alkyl-3-methylimidazolium chloride ionic liquids and salts

NASA Astrophysics Data System (ADS)

Belchior, Diana C. V.; Sintra, Tânia E.; Carvalho, Pedro J.; Soromenho, Mário R. C.; Esperança, José M. S. S.; Ventura, Sónia P. M.; Rogers, Robin D.; Coutinho, João A. P.; Freire, Mara G.

2018-05-01

This work provides a comprehensive evaluation of the effect of the cation alkyl side chain length of the 1-alkyl-3-methylimidazolium chloride series ([CnC1im]Cl, n = 2-14) of ionic liquids (ILs) on their capability to form aqueous biphasic systems (ABSs) with salts and self-aggregation derived properties. The liquid-liquid phase behavior of ternary systems composed of [CnC1im]Cl, water, and K3PO4 or K2CO3 and the respective Setschenow salting-out coefficients (ks), a quantitative measure of the two-phase formation ability, were determined. An odd-even effect in the ks values along the number of methylene groups of the longest IL cation alkyl side chain was identified for the ABS formed by K2CO3, a weaker salting-out agent where the phenomenon is clearly identified. In general, cations with even alkyl side chains, being likely to display higher molar volumes, are more easily salted-out and thus more prone to undergo phase separation. The odd-even effect in the ks values is, however, more significant in ILs up to n = 6, where the nanostructuration/nanosegregation of ILs plays a less relevant role. Still, with the [CnC1im]Cl (n = 7-14) series of ILs, an odd-even effect was also identified in the ILs' ionization degree, molar conductivity, and conductivity at infinite dilution. In summary, it is shown here that the ILs' odd-even effect occurs in IL aqueous solutions and not just in neat ILs, an already well-established phenomenon occurring in a series of ILs' properties described as a result of the orientation of the terminal methyl groups to the imidazolium ring cation and consequent effect in the ILs' cohesive energy.

Approach-related lesions of the sympathetic chain in anterior correction and instrumentation of idiopathic scoliosis

PubMed Central

Adolphs, Bastian; Oberdiek, Denise; Osada, Nani; Liljenqvist, Ulf; Filler, Timm J.; Marziniak, Martin; Bullmann, Viola

2010-01-01

During anterior scoliosis instrumentation with a dual-rod system, the vertebrae are dissected anterolaterally. After surgery, some patients report a change in temperature perception and perspiration in the lower extremities. Sympathetic lesions might be an explanation for this. The aim of this clinical study was to investigate sympathetic function after anterior scoliosis instrumentation. A total of 24 female patients with idiopathic scoliosis (mean age at follow-up, 23.8 years) who had undergone anterior instrumentation on average 6.6 years earlier were included. Due to the suspected relevance of the sympathetic L2 ganglion, two groups were created: a T12 group, in which instrumentation down to T12 was carried out (n = 12), and an L3 group, in which instrumentation down to L3 was done (n = 12). Sympathetic function was assessed by measuring skin temperature at the back of the foot, a plantar ninhydrin sweat test and sympathetic skin responses (SSRs) following electrical stimulation. The side on which the surgical approach was carried out was compared with the contralateral, control side. Health-related quality of life was investigated using the Scoliosis Research Society SRS-22 patient questionnaire. In the T12 group, mean temperatures of 29.6°C on the side of the approach versus 29.5°C on the control side were measured (P > 0.05); in the L3 group, the mean temperatures were 33.2°C on the approach side versus 30.5°C on the control side (P = 0.001). A significant difference between the T12 group and the L3 group (P < 0.001) was observed on the approach side, but not on the control side (P = 0.15). The ninhydrin sweat test showed reduced perspiration in 11 of 12 patients in the L3 group on the approach side in comparison with the control side (P = 0.002). In the T12 group, no significant differences were noted between the left and right feet. SSRs differed significantly between the two groups (P = 0.005). They were detected in all nine analyzable patients in the T12 group on both sides. In the L3 group, they were found on the approach side only in 4 of 11 analyzable patients versus 11 patients on the control side. The results of the SRS-22 questionnaire did not show any significant differences between the two groups. In conclusion, anterior scoliosis instrumentation with a dual-rod system including vertebrae down to L3 regularly leads to lesions in the sympathetic trunk. These are detectable with an increase in temperature, reduced perspiration and reduced SSRs. The caudal level of instrumentation (T12 vs. L3) has an impact on the extent of impairment, supporting the suspected importance of the L2 ganglion. The clinical outcome does not seem to be significantly limited by sympathetic trunk lesions. PMID:20502925

The effect of the amino-acid side chains on the energy profiles for ion transport in the gramicidin A channel.

PubMed

Etchebest, C; Pullman, A

1985-02-01

Computations on the energy profiles for Na+ in the gramicidin A (GA) channel have been extended by introducing the effect, previously neglected, of the amino acid side chains of GA, fixed in their most stable conformations. The calculations have been performed in two approximations: 1) with the ethanolamine tail fixed in its most stable conformation, 2) with the tail allowed to optimize its conformation upon the progression of the ion. In both approximations the overall shape of the energy profile is very similar to that obtained in the absence of the side chains. One observes, however, a general lowering of the profile upon the adjunction of the side chains. The analysis of the factors responsible for this energy lowering indicates that it is due essentially to the electrostatic and polarisation components of the interaction which interplay differently, however, in the different parts of the channel. A particular role is attributed in this respect to the tryptophan residues of GA. The role of the 4 tryptophans present, Trp 15, 13, 11 and 9, is individualized by stripping of one of them at a time. The strongest effect on the energy deepening is due to Trp 13 and is particularly prominent in the entrance zone at 14.5A from the center of the channel. The result indicates the possibility of investigating theoretically the effect on the energy profiles of the substitution of the "natural" side chain by others.

2,4,6,8-Tetra-kis(2-fluoro-phen-yl)-3,7-diaza-bicyclo-[3.3.1]nonan-9-one.

PubMed

Park, Dong Ho; Ramkumar, V; Parthiban, P

2013-02-01

The title compound, C(31)H(24)F(4)N(2)O, exists in a chair-boat conformation with an equatorial orientation of the 2-fluoro-phenyl groups on both sides of the secondary amino group of the chair form. The benzene rings in the 'chair' part are inclined to each other at 19.4 (1)°, while the equivalent angle between the benzene rings in the 'boat' part is 75.6 (1)°. One F atom was treated as disordered over two positions in a 0.838 (4):0.162 (4) ratio. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains along [001] and these chains are held together via weak N-H⋯F and C-H⋯F inter-actions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hua; Zhou, Feng; Ren, Gerui

In this article, the SuFEx-based polycondensation between bisalkylsulfonyl fluorides (AA monomers) and bisphenol bis(t-butyldimethylsilyl) ethers (BB monomers) using [Ph 3P=N-PPh 3] +[HF 2] - as the catalyst is described. The AA monomers were prepared via the highly reliable Michael addition of ethenesulfonyl fluoride and amines/anilines while the BB monomers were obtained from silylation of bisphenols by t-butyldimethylsilyl chloride. With these reactions, a remarkable diversity of monomeric building blocks was achieved by exploiting readily available amines, anilines, and bisphenols as starting materials. The SuFEx-based polysulfonate formation reaction exhibited excellent efficiency and functional group tolerance, producing polysulfonates with a variety of sidemore » chain functionalities in >99 % conversion within 10 min to 1 h. When bearing an orthogonal group on the side chain, the polysulfonates can be further functionalized via click-chemistry-based post-polymerization modification.« less

Mapping the Geometric Evolution of Protein Folding Motor.

PubMed

Jerath, Gaurav; Hazam, Prakash Kishore; Shekhar, Shashi; Ramakrishnan, Vibin

2016-01-01

Polypeptide chain has an invariant main-chain and a variant side-chain sequence. How the side-chain sequence determines fold in terms of its chemical constitution has been scrutinized extensively and verified periodically. However, a focussed investigation on the directive effect of side-chain geometry may provide important insights supplementing existing algorithms in mapping the geometrical evolution of protein chains and its structural preferences. Geometrically, folding of protein structure may be envisaged as the evolution of its geometric variables: ϕ, and ψ dihedral angles of polypeptide main-chain directed by χ1, and χ2 of side chain. In this work, protein molecule is metaphorically modelled as a machine with 4 rotors ϕ, ψ, χ1 and χ2, with its evolution to the functional fold is directed by combinations of its rotor directions. We observe that differential rotor motions lead to different secondary structure formations and the combinatorial pattern is unique and consistent for particular secondary structure type. Further, we found that combination of rotor geometries of each amino acid is unique which partly explains how different amino acid sequence combinations have unique structural evolution and functional adaptation. Quantification of these amino acid rotor preferences, resulted in the generation of 3 substitution matrices, which later on plugged in the BLAST tool, for evaluating their efficiency in aligning sequences. We have employed BLOSUM62 and PAM30 as standard for primary evaluation. Generation of substitution matrices is a logical extension of the conceptual framework we attempted to build during the development of this work. Optimization of matrices following the conventional routines and possible application with biologically relevant data sets are beyond the scope of this manuscript, though it is a part of the larger project design.

Zinc Binding and Dimerization of Streptococcus pyogenes Pyrogenic Exotoxin C Are Not Essential for T-Cell Stimulation

DTIC Science & Technology

2003-03-14

streptococcal superantigen binding to MHCII on the surface of cells (7–9), suggesting an essential role in both MHCII molecular recognition and TCR-mediated...extent, mutations of side chains found in a second conserved MHCII alpha-chain-binding site consisting of a hydrophobic surface loop decreased T-cell...fraction of dimer is present at T-cell stimulatory concentrations of Spe-C following mutation of the unpaired side chain of cys- teine at residue 27 to

Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain.

PubMed

Merle, B; Durussel, L; Delmas, P D; Clézardin, P

1999-12-01

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains. Copyright 1999 Wiley-Liss, Inc.

Crystal structures of the class D beta-lactamase OXA-13 in the native form and in complex with meropenem.

PubMed

Pernot, L; Frénois, F; Rybkine, T; L'Hermite, G; Petrella, S; Delettré, J; Jarlier, V; Collatz, E; Sougakoff, W

2001-07-20

The therapeutic problems posed by class D beta-lactamases, a family of serine enzymes that hydrolyse beta-lactam antibiotics following an acylation-deacylation mechanism, are increased by the very low level of sensitivity of these enzymes to beta-lactamase inhibitors. To gain structural and mechanistic insights to aid the design of new inhibitors, we have determined the crystal structure of OXA-13 from Pseudomonas aeruginosa in the apo form and in complex with the carbapenem meropenem. The native form consisted of a dimer displaying an overall organisation similar to that found in the closely related enzyme OXA-10. In the acyl-enzyme complex, the positioning of the antibiotic appeared to be ensured mainly by (i) the covalent acyl bond and (ii) a strong salt-bridge involving the carboxylate moiety of the drug. Comparison of the structures of OXA-13 in the apo form and in complex with meropenem revealed an unsuspected flexibility in the region of the essential serine 115 residue, with possible consequences for the catalytic properties of the enzyme. In the apo form, the Ser115 side-chain is oriented outside the active site, whereas the general base Lys70 adopts a conformation that seems to be incompatible with the activation of the catalytic water molecule required for the deacylation step. In the OXA-13:meropenem complex, a 3.5 A movement of the backbone of the 114-116 loop towards the side-chain of Lys70 was observed, which seems to be driven by a displacement of the neighbouring 91-104 loop and which results in the repositioning of the side-chain hydroxyl group of Ser115 toward the catalytic centre. Concomitantly, the side-chain of Lys70 is forced to curve in the direction of the deacylating water molecule, which is then strongly bound and activated by this residue. However, a distance of ca 5 A separates the catalytic water molecule from the acyl carbonyl group of meropenem, a structural feature that accounts for the inhibition of OXA-13 by this drug. Finally, the low level of penicillinase activity revealed by the kinetic analysis of OXA-13 could be related to the specific presence in position 73 of a serine residue located close to the general base Lys70, which results in a decrease of the number of hydrogen-bonding interactions stabilising the catalytic water molecule. Copyright 2001 Academic Press.

Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the high-density lipoprotein receptor SR-BI.

PubMed

Yu, Miao; Lau, Thomas Y; Carr, Steven A; Krieger, Monty

2012-12-18

The high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys(321)-Pro(322)-Cys(323) (CPC) motif and connect Cys(280) to Cys(334). We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys(384) to HDL binding and lipid uptake. The effects of CPC mutations on activity were context-dependent. Full wild-type (WT) activity required Pro(322) and Cys(323) only when Cys(321) was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX, or XXX mutants (X ≠ WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys(323) is deleterious, perhaps because of aberrant disulfide bond formation. Pro(322) may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for normal activity. C(384)X (X = S, T, L, Y, G, or A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (enhanced binding, weakened uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C(384)X mutants were BLT-1-resistant, supporting the proposal that Cys(384)'s thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories.

Single-Point Mutation with a Rotamer Library Toolkit: Toward Protein Engineering.

PubMed

Pottel, Joshua; Moitessier, Nicolas

2015-12-28

Protein engineers have long been hard at work to harness biocatalysts as a natural source of regio-, stereo-, and chemoselectivity in order to carry out chemistry (reactions and/or substrates) not previously achieved with these enzymes. The extreme labor demands and exponential number of mutation combinations have induced computational advances in this domain. The first step in our virtual approach is to predict the correct conformations upon mutation of residues (i.e., rebuilding side chains). For this purpose, we opted for a combination of molecular mechanics and statistical data. In this work, we have developed automated computational tools to extract protein structural information and created conformational libraries for each amino acid dependent on a variable number of parameters (e.g., resolution, flexibility, secondary structure). We have also developed the necessary tool to apply the mutation and optimize the conformation accordingly. For side-chain conformation prediction, we obtained overall average root-mean-square deviations (RMSDs) of 0.91 and 1.01 Å for the 18 flexible natural amino acids within two distinct sets of over 3000 and 1500 side-chain residues, respectively. The commonly used dihedral angle differences were also evaluated and performed worse than the state of the art. These two metrics are also compared. Furthermore, we generated a family-specific library for kinases that produced an average 2% lower RMSD upon side-chain reconstruction and a residue-specific library that yielded a 17% improvement. Ultimately, since our protein engineering outlook involves using our docking software, Fitted/Impacts, we applied our mutation protocol to a benchmarked data set for self- and cross-docking. Our side-chain reconstruction does not hinder our docking software, demonstrating differences in pose prediction accuracy of approximately 2% (RMSD cutoff metric) for a set of over 200 protein/ligand structures. Similarly, when docking to a set of over 100 kinases, side-chain reconstruction (using both general and biased conformation libraries) had minimal detriment to the docking accuracy.

Evaluating Force Fields for the Computational Prediction of Ionized Arginine and Lysine Side-Chains Partitioning into Lipid Bilayers and Octanol.

PubMed

Sun, Delin; Forsman, Jan; Woodward, Clifford E

2015-04-14

Abundant peptides and proteins containing arginine (Arg) and lysine (Lys) amino acids can apparently permeate cell membranes with ease. However, the mechanisms by which these peptides and proteins succeed in traversing the free energy barrier imposed by cell membranes remain largely unestablished. Precise thermodynamic studies (both theoretical and experimental) on the interactions of Arg and Lys residues with model lipid bilayers can provide valuable clues to the efficacy of these cationic peptides and proteins. We have carried out molecular dynamics simulations to calculate the interactions of ionized Arg and Lys side-chains with the zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer for 10 widely used lipid/protein force fields: CHARMM36/CHARMM36, SLIPID/AMBER99SB-ILDN, OPLS-AA/OPLS-AA, Berger/OPLS-AA, Berger/GROMOS87, Berger/GROMOS53A6, GROMOS53A6/GROMOS53A6, nonpolarizable MARTINI, polarizable MARTINI, and BMW MARTINI. We performed umbrella sampling simulations to obtain the potential of mean force for Arg and Lys side-chains partitioning from water to the bilayer interior. We found significant differences between the force fields, both for the interactions between side-chains and bilayer surface, as well as the free energy cost for placing the side-chain at the center of the bilayer. These simulation results were compared with the Wimley-White interfacial scale. We also calculated the free energy cost for transferring ionized Arg and Lys side-chains from water to both dry and wet octanol. Our simulations reveal rapid diffusion of water molecules into octanol whereby the equilibrium mole fraction of water in the wet octanol phase was ∼25%. Surprisingly, our free energy calculations found that the high water content in wet octanol lowered the water-to-octanol partitioning free energies for cationic residues by only 0.6 to 0.7 kcal/mol.

Comprehensive Study on the Impact of the Cation Alkyl Side Chain Length on the Solubility of Water in Ionic Liquids.

PubMed

Kurnia, Kiki A; Neves, Catarina M S S; Freire, Mara G; Santos, Luís M N B F; Coutinho, João A P

2015-10-01

A comprehensive study on the phase behaviour of two sets of ionic liquids (ILs) and their interactions with water is here presented through combining experimental and theoretical approaches. The impact of the alkyl side chain length and the cation symmetry on the water solubility in the asymmetric [C N- 1 C 1 im][NTf 2 ] and symmetric [C N- 1 C N- 1 im][NTf 2 ] series of ILs ( N up to 22), from 288.15 K to 318.15 K and at atmospheric pressure, was studied. The experimental data reveal that the solubility of water in ILs with an asymmetric cation is higher than in those with the symmetric isomer. Several trend shifts on the water solubility as a function of the alkyl side chain length were identified, namely at [C 6 C 1 im][NTf 2 ] for asymmetric ILs and at [C 4 C 4 im][NTf 2 ] and [C 7 C 7 im][NTf 2 ] for the symmetric ILs. To complement the experimental data and to further investigate the molecular-level mechanisms behind the dissolution process, Density Functional Theory calculations, using the Conductor-like Screening Model for Real Solvents (COSMO-RS) and the Electrostatic potential-derived CHelpG, were performed. The COSMO-RS model is able to qualitatively predict water solubility as function of temperature and alkyl chain lengths of both symmetric and asymmetric cations. Furthermore, the model is also capable to predict the somewhat higher water solubility in the asymmetric cation, as well as the trend shift as function of alkyl chain lengths experimentally observed. Both COSMO-RS and the electrostatic potential-derived CHelpG show that the interactions of water and the IL cation take place on the IL polar region, namely on the aromatic head and adjacent methylene groups what explains the differences in water solubility observed for cations with different chain lengths. Furthermore, the CHelpG calculations for the isolated cations in the gas phase indicates that the trend shift of water solubility as function of alkyl chain lengths and the difference of water solubility in symmetric may also result from the partial positive charge distribution/contribution of the cation.

Structure–Function Studies of Hydrophobic Residues That Clamp a Basic Glutamate Side Chain during Catalysis by Triosephosphate Isomerase

PubMed Central

2016-01-01

Kinetic parameters are reported for the reactions of whole substrates (kcat/Km, M–1 s–1) (R)-glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) and for the substrate pieces [(kcat/Km)E·HPi/Kd, M–2 s–1] glycolaldehyde (GA) and phosphite dianion (HPi) catalyzed by the I172A/L232A mutant of triosephosphate isomerase from Trypanosoma brucei brucei (TbbTIM). A comparison with the corresponding parameters for wild-type, I172A, and L232A TbbTIM-catalyzed reactions shows that the effect of I172A and L232A mutations on ΔG⧧ for the wild-type TbbTIM-catalyzed reactions of the substrate pieces is nearly the same as the effect of the same mutations on TbbTIM previously mutated at the second side chain. This provides strong evidence that mutation of the first hydrophobic side chain does not affect the functioning of the second side chain in catalysis of the reactions of the substrate pieces. By contrast, the effects of I172A and L232A mutations on ΔG⧧ for wild-type TbbTIM-catalyzed reactions of the whole substrate are different from the effect of the same mutations on TbbTIM previously mutated at the second side chain. This is due to the change in the rate-determining step that determines the barrier to the isomerization reaction. X-ray crystal structures are reported for I172A, L232A, and I172A/L232A TIMs and for the complexes of these mutants to the intermediate analogue phosphoglycolate (PGA). The structures of the PGA complexes with wild-type and mutant enzymes are nearly superimposable, except that the space opened by replacement of the hydrophobic side chain is occupied by a water molecule that lies ∼3.5 Å from the basic side chain of Glu167. The new water at I172A mutant TbbTIM provides a simple rationalization for the increase in the activation barrier ΔG⧧ observed for mutant enzyme-catalyzed reactions of the whole substrate and substrate pieces. By contrast, the new water at the L232A mutant does not predict the decrease in ΔG⧧ observed for the mutant enzyme-catalyzed reactions of the substrate piece GA. PMID:27149328

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

NASA Astrophysics Data System (ADS)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng pectin on galectin-3 and its structure-activity relationship.

PubMed

Gao, Xiaoge; Zhi, Yuan; Sun, Lin; Peng, Xiaoxia; Zhang, Tao; Xue, Huiting; Tai, Guihua; Zhou, Yifa

2013-11-22

Pectin has been shown to inhibit the actions of galectin-3, a β-galactoside-binding protein associated with cancer progression. The structural features of pectin involved in this activity remain unclear. We investigated the effects of different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination, cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T-cells. RG-I-4 specifically bound to the carbohydrate recognition domain of galectin-3 with a dissociation constant of 22.2 nm, which was determined by surface plasmon resonance analysis. The structure-activity relationship of RG-I-4 was investigated by modifying the structure through various enzymatic and chemical methods followed by activity tests. The results showed that (a) galactan side chains were essential to the activity of RG-I-4, whereas arabinan side chains positively or negatively regulated the activity depending on their location within the RG-I-4 molecule. (b) The activity of galactan chain was proportional to its length up to 4 Gal residues and largely unchanged thereafter. (c) The majority of galactan side chains in RG-I-4 were short with low activities. (d) The high activity of RG-I-4 resulted from the cooperative action of these side chains. (e) The backbone of the molecule was very important to RG-I-4 activity, possibly by maintaining a structural conformation of the whole molecule. (f) The isolated backbone could bind galectin-3, which was insensitive to lactose treatment. The novel discovery that the side chains and backbone play distinct roles in regulating RG-I-4 activity is valuable for producing highly active pectin-based galectin-3 inhibitors.

Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

PubMed

Liu, X-D; Gao, N; Qiao, H-L

2011-03-01

Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins. We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test. Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear structure and R1 side-chain contribute to IgE recognition. There exists cross-reactivity between cephalosporins and penicillins; patients allergic to several penicillins are more likely to develop allergic reaction to cephalosporins; due to sensitization to the similar structural characteristics (nuclear and R1 side-chain), penicillin-allergic patients may develop cross-allergic reactions with not only first-generation but also third-generation cephalosporins.

Targeting radiosensitizers to DNA by attachment of an intercalating group: Nitroimidazole-linked phenanthridines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cowan, D.S.; Panicucci, R.; McClelland, R.A.

The nitroimidazole-linked phenanthridine series of compounds (NLP-1, 2, and 3) were synthesized under the assumption that it should be possible to enhance the molar efficiency of 2-nitroimidazoles as hypoxic cell radiosensitizers and cytotoxins by targeting them to their likely site of action, DNA. The targeting group chosen was the phenanthridine moiety, the major component of the classical DNA intercalating compound, ethidium bromide. The sole difference between the compounds is the length of the hydrocarbon chain linking the nitroimidazole to the phenanthridine. The phenanthridine group with a three-carbon side chain, P-1, was also synthesized to allow studies on the effect ofmore » the targeting group by itself. The ability of the compounds to bind to DNA is inversely proportional to their linker chain length with binding constant values ranging from approximately 1 {times} 10(5) mol-1 for NLP-2 to 6 {times} 10(5) mol-1 for NLP-3. The NLP compounds show selective toxicity to hypoxic cells at 37 degrees C at external drug concentrations 10-40 times lower than would be required for untargeted 2-nitroimidazoles such as misonidazole in vitro. Toxicity to both hypoxic and aerobic cells is dependent on the linker chain: the shorter the chain, the greater the toxicity. In addition, the NLP compounds radiosensitize hypoxic cells at external drug concentrations as low as 0.05 mM with almost the full oxygen effect being observed at a concentration of 0.5 mM. These concentrations are 10-100 times lower than would be required for similar radiosensitization using misonidazole. Radiosensitizing ability is independent of linker chain length. The present compounds represent prototypes for further studies of the efficacy and mechanism of action of 2-nitroimidazoles targeted to DNA by linkage to an intercalating group.« less

Silicone derivatives for contact lenses: functionalization, chemical characterization, and cell compatibility assessment.

PubMed

Migonney, V; Lacroix, M D; Ratner, B D; Jozefowicz, M

1995-01-01

Epoxy ring-opening functionalization of polymers at random sites along chains with various chemical groups has been demonstrated. The reaction is performed in an aqueous solution under mild conditions in order to minimize degradation of the macromolecular chains. Silicone lenses made of copolymers with epoxy side chains were functionalized with 4-hydroxybutyric acid, sodium salt. The carboxylated silicone derivatives were characterized by ESCA and radiotracers. A mean value of 30% reaction yield was concluded, based upon data from both methods; nevertheless, the latter can be improved up to 50% or more if the conditions of preparation of the epoxydized silicone lenses are optimized. Derivatized silicones were coated in the wells of culture plates to evaluate the cell compatibility of these new polymers with a fibroblast cell line (McCoy's). No cellular toxicity was observed.

Macromolecular properties of cepacian in water and in dimethylsulfoxide.

PubMed

Herasimenka, Yury; Cescutti, Paola; Sampaio Noguera, Carlos E; Ruggiero, Josè R; Urbani, Ranieri; Impallomeni, Giuseppe; Zanetti, Flavio; Campidelli, Stéphane; Prato, Maurizio; Rizzo, Roberto

2008-01-14

Cepacian is the exopolysaccharide produced by the majority of the so far investigated clinical strains of the Burkholderia cepacia complex. This is a group of nine closely related bacterial species that might cause serious lung infections in cystic fibrosis patients, in some cases leading to death. In this paper the aggregation ability and the conformational properties of cepacian chain were investigated to understand its role in biofilm formation. Viscosity and atomic force microscopy studies in water and in mixed (dimethylsulfoxide/water) solvent indicated the formation of double stranded molecular structures in aqueous solutions. Inter-residue short distances along cepacian chain were investigated by NOE NMR, which showed that two side chains of cepacian were not conformationally free due to strong interactions with the polymer backbone. These interactions were attributed to hydrogen bonding and contributed to structure rigidity.

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa.

PubMed

Takeoka, Yusuke; Tanino, Tetsuya; Sekiguchi, Mitsuaki; Yonezawa, Shuji; Sakagami, Masahiro; Takahashi, Fumiyo; Togame, Hiroko; Tanaka, Yoshikazu; Takemoto, Hiroshi; Ichikawa, Satoshi; Matsuda, Akira

2014-05-08

It is urgent to develop novel anti-Pseudomonas agents that should also be active against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum of muraymycins toward P. aeruginosa was investigated by the systematic structure-activity relationship study. It was revealed that two functional groups, a lipophilic side chain and a guanidino group, at the accessory moiety of muraymycins were important for the anti-Pseudomonas activity, and analogue 29 exhibited antibacterial activity against a range of P. aeruginosa strains with the minimum inhibitory concentration values of 4-8 μg/mL.

Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa

PubMed Central

2014-01-01

It is urgent to develop novel anti-Pseudomonas agents that should also be active against multidrug resistant P. aeruginosa. Expanding the antibacterial spectrum of muraymycins toward P. aeruginosa was investigated by the systematic structure–activity relationship study. It was revealed that two functional groups, a lipophilic side chain and a guanidino group, at the accessory moiety of muraymycins were important for the anti-Pseudomonas activity, and analogue 29 exhibited antibacterial activity against a range of P. aeruginosa strains with the minimum inhibitory concentration values of 4–8 μg/mL. PMID:24900879

Compounds having aromatic rings and side-chain amide-functionality and a method for transporting monovalent anions across biological membranes using the same

DOEpatents

Davis, Jeffery T [College Park, MD; Sidorov, Vladimir [Richmond, VA; Kotch, Frank W [New Phila., PA

2008-04-08

A compound containing at least two aromatic rings covalently bonded together, with each aromatic ring containing at least one oxyacetamide-based side chain, the compound being capable of forming a chloride ion channel across a lipid bilayer, and transporting chloride ion across the lipid bilayer.

Novel Semiconducting Polymers for Highly Efficient Solar Energy Harvesting

DTIC Science & Technology

2014-03-11

pyrrole -4,6-dione, a well known electron-deficient monomer, to obtain the new copolymer PTTATPD-1 for comparison in physical properties. The number...bulk side chain showed a PCE about 0.6%; PTTATT-4 with 2- ethyldedocyl side chain showed a PCE about 3.0% and the copolymer with thieno[3,4-c] pyrrol

Arabidopsis GUX Proteins Are Glucuronyltransferases Responsible for the Addition of Glucuronic Acid Side Chains onto Xylan

EPA Science Inventory

Xylan, the second most abundant cell wall polysaccharide, is composed of a linear backbone of β-(1,4)-linked xylosyl residues that are often substituted with sugar side chains, such as glucuronic acid (GlcA) and methylglucuronic acid (MeGlcA). It has recently been shown that muta...

Polymer non-fullerene solar cells of vastly different efficiencies for minor side-chain modification: impact of charge transfer, carrier lifetime, morphology and mobility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awartani, Omar M.; Gautam, Bhoj; Zhao, Wenchao

The performance of the 11.25% efficient PBDB-T : ITIC system degraded to 4.35% after a minor side-chain modification in PBDB-O : ITIC. In this study, the underlying reasons behind this vast difference in efficiencies are investigated.

Ring structure modifications of phenylalanine 19 increase fibrillation kinetics and reduce toxicity of amyloid β (1-40).

PubMed

Korn, Alexander; Surendran, Dayana; Krueger, Martin; Maiti, Sudipta; Huster, Daniel

2018-05-24

We investigated the influence of the chemical structure of the phenylalanine side chain in position 19 of the 40 residue amyloid β peptide. Side chain modifications in this position yielded fibrils of essentially unaltered morphology, structure, and dynamics, but significantly increased fibrillation kinetics and diminished the toxicity of the peptides.

Side-chain Liquid Crystal Polymers (SCLCP): Methods and Materials. An Overview

PubMed Central

Ganicz, Tomasz; Stańczyk, Włodzimierz

2009-01-01

This review focuses on recent developments in the chemistry of side chain liquid crystal polymers. It concentrates on current trends in synthetic methods and novel, well defined structures, supramolecular arrangements, properties, and applications. The review covers literature published in this century, apart from some areas, such as dendritic and elastomeric systems, which have been recently reviewed.

Polymer non-fullerene solar cells of vastly different efficiencies for minor side-chain modification: impact of charge transfer, carrier lifetime, morphology and mobility

DOE PAGES

Awartani, Omar M.; Gautam, Bhoj; Zhao, Wenchao; ...

2018-01-01

The performance of the 11.25% efficient PBDB-T : ITIC system degraded to 4.35% after a minor side-chain modification in PBDB-O : ITIC. In this study, the underlying reasons behind this vast difference in efficiencies are investigated.

Solvent polarity effects on supramolecular chirality of a polyfluorene-thiophene copolymer.

PubMed

Hirahara, Takashi; Yoshizawa-Fujita, Masahiro; Takeoka, Yuko; Rikukawa, Masahiro

2018-06-01

This study demonstrates the supramolecular chirality control of a conjugated polymer via solvent polarity. We designed and synthesized a chiral polyfluorene-thiophene copolymer having two different chiral side chains at the 9-position of the fluorene unit. Chiral cyclic and alkyl ethers with different polarities were selected as the chiral side chains. The sign of the circular dichroism spectra in the visible wavelength region was affected by the solvent system, resulting from the change of supramolecular structure. The estimation of the solubility parameter revealed that the solubility difference of the side chains contributed to the change of the circular dichroism sign, which was also observed in spin-coated films prepared from good solvents having different polarities. © 2018 Wiley Periodicals, Inc.

Pressure dependence of side chain 13C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

PubMed

Beck Erlach, Markus; Koehler, Joerg; Crusca, Edson; Munte, Claudia E; Kainosho, Masatsune; Kremer, Werner; Kalbitzer, Hans Robert

2017-10-01

For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of 13 C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH 2 (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B 1 and B 2 is dependent on the type of atom and amino acid studied. For H N , N and C α the first order pressure coefficient B 1 is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically 13 C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.

Efficient peptide ligation between allyl-protected Asp and Cys followed by palladium-mediated deprotection.

PubMed

Kamo, Naoki; Hayashi, Gosuke; Okamoto, Akimitsu

2018-04-24

An efficient method for peptide ligation between C-terminal Asp(OAllyl) and N-terminal Cys has been developed. Peptide ligation and removal of the allyl group at the Asp carboxylate side chain proceeded in one pot by adding a small amount of Pd/TPPTS complex. Based on this efficient synthetic method, PEP-19 (61 amino acids), which is highly expressed in Purkinje cells, was synthesized.

Biologically Active Polymeric Coating Materials

DTIC Science & Technology

1975-04-01

unsaturated alkyds , or through a condensation reaction of an organometallic oxide and a resin containing carboxylic acid groups as side chains. The...extend the service life of antifouling coatings by means of polymerization of toxicant into paint resins . The coating binder is so constructed that the...from styrene (s6) and polyester (P54, figure 5) organometallic resins . To date, the antifouling performance of epoxy (WS 52B, figure 6) and

An Experimental and Computational Study of the Gas-Phase Acidities of the Common Amino Acid Amides.

PubMed

Plummer, Chelsea E; Stover, Michele L; Bokatzian, Samantha S; Davis, John T M; Dixon, David A; Cassady, Carolyn J

2015-07-30

Using proton-transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer and correlated molecular orbital theory at the G3(MP2) level, gas-phase acidities (GAs) and the associated structures for amides corresponding to the common amino acids have been determined for the first time. These values are important because amino acid amides are models for residues in peptides and proteins. For compounds whose most acidic site is the C-terminal amide nitrogen, two ions populations were observed experimentally with GAs that differ by 4-7 kcal/mol. The lower energy, more acidic structure accounts for the majority of the ions formed by electrospray ionization. G3(MP2) calculations predict that the lowest energy anionic conformer has a cis-like orientation of the [-C(═O)NH](-) group whereas the higher energy, less acidic conformer has a trans-like orientation of this group. These two distinct conformers were predicted for compounds with aliphatic, amide, basic, hydroxyl, and thioether side chains. For the most acidic amino acid amides (tyrosine, cysteine, tryptophan, histidine, aspartic acid, and glutamic acid amides) only one conformer was observed experimentally, and its experimental GA correlates with the theoretical GA related to side chain deprotonation.

Ionic liquids at the surface of graphite: Wettability and structure

NASA Astrophysics Data System (ADS)

Bordes, Emilie; Douce, Laurent; Quitevis, Edward L.; Pádua, Agílio A. H.; Costa Gomes, Margarida

2018-05-01

The aim of this work is to provide a better understanding of the interface between graphite and different molecular and ionic liquids. Experimental measurements of the liquid surface tension and of the graphite-liquid contact angle for sixteen ionic liquids and three molecular liquids are reported. These experimental values allowed the calculation of the solid/liquid interfacial energy that varies, for the ionic liquids studied, between 14.5 mN m-1 for 1-ethyl-3-methylimidazolium dicyanamide and 37.8 mN m-1 for 3-dodecyl-1-(naphthalen-1-yl)-1H-imidazol-3-ium tetrafluoroborate. Imidazolium-based ionic liquids with large alkyl side-chains or functionalized with benzyl groups seem to interact more favourably with freshly peeled graphite surfaces. Even if the interfacial energy seems a good descriptor to assess the affinity of a liquid for a carbon-based solid material, we conclude that both the surface tension of the liquid and the contact angle between the liquid and the solid can be significant. Molecular dynamics simulations were used to investigate the ordering of the ions near the graphite surface. We conclude that the presence of large alkyl side-chains in the cations increases the ordering of ions at the graphite surface. Benzyl functional groups in the cations lead to a large affinity towards the graphite surface.

Bile alcohols function as the ligands of membrane-type bile acid-activated G protein-coupled receptor

PubMed Central

Iguchi, Yusuke; Yamaguchi, Masafumi; Sato, Hiroyuki; Kihira, Kenji; Nishimaki-Mogami, Tomoko; Une, Mizuho

2010-01-01

TGR5 is a G protein-coupled receptor that is activated by bile acids, resulting in an increase in cAMP levels and the subsequent modulation of energy expenditure in brown adipose tissue and muscle. Therefore, the development of a TGR5-specific agonist could lead to the prevention and treatment of various metabolic disorders related to obesity. In the present study, we evaluated the ability of bile alcohols, which are structurally and physiologically similar to bile acids and are produced as the end products of cholesterol catabolism in evolutionarily primitive vertebrates, to act as TGR5 agonists. In a cell-based reporter assay and a cAMP production assay performed in vitro, most bile alcohols with a side chain containing hydroxyl group(s) were highly efficacious agonists for TGR5 comparable to its most potent ligand in the naturally occurring bile acid, lithocholic acid. However, the abilities of the bile alcohols to activate TGR5 varied with the position and number of the hydroxyl substituent in the side chain. Additionally, the conformation of the steroidal nucleus of bile alcohols is also important for its activity as a TGR5 agonist. Thus, we have provided new insights into the structure-activity relationships of bile alcohols as TGR5 agonists. PMID:20023205

Hypothesis of Lithocoding: Origin of the Genetic Code as a "Double Jigsaw Puzzle" of Nucleobase-Containing Molecules and Amino Acids Assembled by Sequential Filling of Apatite Mineral Cellules.

PubMed

Skoblikow, Nikolai E; Zimin, Andrei A

2016-05-01

The hypothesis of direct coding, assuming the direct contact of pairs of coding molecules with amino acid side chains in hollow unit cells (cellules) of a regular crystal-structure mineral is proposed. The coding nucleobase-containing molecules in each cellule (named "lithocodon") partially shield each other; the remaining free space determines the stereochemical character of the filling side chain. Apatite-group minerals are considered as the most preferable for this type of coding (named "lithocoding"). A scheme of the cellule with certain stereometric parameters, providing for the isomeric selection of contacting molecules is proposed. We modelled the filling of cellules with molecules involved in direct coding, with the possibility of coding by their single combination for a group of stereochemically similar amino acids. The regular ordered arrangement of cellules enables the polymerization of amino acids and nucleobase-containing molecules in the same direction (named "lithotranslation") preventing the shift of coding. A table of the presumed "LithoCode" (possible and optimal lithocodon assignments for abiogenically synthesized α-amino acids involved in lithocoding and lithotranslation) is proposed. The magmatic nature of the mineral, abiogenic synthesis of organic molecules and polymerization events are considered within the framework of the proposed "volcanic scenario".

Locating active-site hydrogen atoms in d-xylose isomerase: Time-of-flight neutron diffraction

PubMed Central

Katz, Amy K.; Li, Xinmin; Carrell, H. L.; Hanson, B. Leif; Langan, Paul; Coates, Leighton; Schoenborn, Benno P.; Glusker, Jenny P.; Bunick, Gerard J.

2006-01-01

Time-of-flight neutron diffraction has been used to locate hydrogen atoms that define the ionization states of amino acids in crystals of d-xylose isomerase. This enzyme, from Streptomyces rubiginosus, is one of the largest enzymes studied to date at high resolution (1.8 Å) by this method. We have determined the position and orientation of a metal ion-bound water molecule that is located in the active site of the enzyme; this water has been thought to be involved in the isomerization step in which d-xylose is converted to d-xylulose or d-glucose to d-fructose. It is shown to be water (rather than a hydroxyl group) under the conditions of measurement (pH 8.0). Our analyses also reveal that one lysine probably has an −NH2-terminal group (rather than NH3+). The ionization state of each histidine residue also was determined. High-resolution x-ray studies (at 0.94 Å) indicate disorder in some side chains when a truncated substrate is bound and suggest how some side chains might move during catalysis. This combination of time-of-flight neutron diffraction and x-ray diffraction can contribute greatly to the elucidation of enzyme mechanisms. PMID:16707576

The 3'-5' exonuclease of DNA polymerase I of Escherichia coli: contribution of each amino acid at the active site to the reaction.

PubMed Central

Derbyshire, V; Grindley, N D; Joyce, C M

1991-01-01

We have used site-directed mutagenesis to change amino acid side chains that have been shown crystallographically to be in close proximity to a DNA 3' terminus bound at the 3'-5' exonuclease active site of Klenow fragment. Exonuclease assays of the resulting mutant proteins indicate that the largest effects on exonuclease activity result from mutations in a group of carboxylate side chains (Asp355, Asp424 and Asp501) anchoring two divalent metal ions that are essential for exonuclease activity. Another carboxylate (Glu357) within this cluster seems to be less important as a metal ligand, but may play a separate role in catalysis of the exonuclease reaction. A second group of residues (Leu361, Phe473 and Tyr497), located around the terminal base and ribose positions, plays a secondary role, ensuring correct positioning of the substrate in the active site and perhaps also facilitating melting of a duplex DNA substrate by interacting with the frayed 3' terminus. The pH-dependence of the 3'-5' exonuclease reaction is consistent with a mechanism in which nucleophilic attack on the terminal phosphodiester bond is initiated by a hydroxide ion coordinated to one of the enzyme-bound metal ions. PMID:1989882

Genetic selection reveals the role of a buried, conserved polar residue

PubMed Central

Johnson, R. Jeremy; Lin, Shawn R.; Raines, Ronald T.

2007-01-01

The burial of nonpolar surface area is known to enhance markedly the conformational stability of proteins. The contribution from the burial of polar surface area is less clear. Here, we report on the tolerance to substitution of Ser75 of bovine pancreatic ribonuclease (RNase A), a residue that has the unusual attributes of being buried, conserved, and polar. To identify variants that retain biological function, we used a genetic selection based on the intrinsic cytotoxicity of ribonucleolytic activity. Cell growth at 30°C, 37°C, and 44°C correlated with residue size, indicating that the primary attribute of Ser75 is its small size. The side-chain hydroxyl group of Ser75 forms a hydrogen bond with a main-chain nitrogen. The conformational stability of the S75A variant, which lacks this hydrogen bond, was diminished by ΔΔG = 2.5 kcal/mol. Threonine, which can reinstate this hydrogen bond, provided a catalytically active RNase A variant at higher temperatures than did some smaller residues (including aspartate), indicating that a secondary attribute of Ser75 is the ability of its uncharged side chain to accept a hydrogen bond. These results provide insight on the imperatives for the conservation of a buried polar residue. PMID:17656580

Biodegradable polyester films from renewable aleuritic acid: surface modifications induced by melt-polycondensation in air

NASA Astrophysics Data System (ADS)

Jesús Benítez, José; Alejandro Heredia-Guerrero, José; Inmaculada de Vargas-Parody, María; Cruz-Carrillo, Miguel Antonio; Morales-Flórez, Victor; de la Rosa-Fox, Nicolás; Heredia, Antonio

2016-05-01

Good water barrier properties and biocompatibility of long-chain biopolyesters like cutin and suberin have inspired the design of synthetic mimetic materials. Most of these biopolymers are made from esterified mid-chain functionalized ω-long chain hydroxyacids. Aleuritic (9,10,16-trihydroxypalmitic) acid is such a polyhydroxylated fatty acid and is also the major constituent of natural lac resin, a relatively abundant and renewable resource. Insoluble and thermostable films have been prepared from aleuritic acid by melt-condensation polymerization in air without catalysts, an easy and attractive procedure for large scale production. Intended to be used as a protective coating, the barrier's performance is expected to be conditioned by physical and chemical modifications induced by oxygen on the air-exposed side. Hence, the chemical composition, texture, mechanical behavior, hydrophobicity, chemical resistance and biodegradation of the film surface have been studied by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), nanoindentation and water contact angle (WCA). It has been demonstrated that the occurrence of side oxidation reactions conditions the surface physical and chemical properties of these polyhydroxyester films. Additionally, the addition of palmitic acid to reduce the presence of hydrophilic free hydroxyl groups was found to have a strong influence on these parameters.

Hydration of amino acids: FTIR spectra and molecular dynamics studies.

PubMed

Panuszko, Aneta; Adamczak, Beata; Czub, Jacek; Gojło, Emilia; Stangret, Janusz

2015-11-01

The hydration of selected amino acids, alanine, glycine, proline, valine, isoleucine and phenylalanine, has been studied in aqueous solutions by means of FTIR spectra of HDO isotopically diluted in H2O. The difference spectra procedure and the chemometric method have been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. To support interpretation of obtained spectral results, molecular dynamics simulations of amino acids were performed. The structural-energetic characteristic of these solute-affected water molecules shows that, on average, water affected by amino acids forms stronger and shorter H-bonds than those in pure water. Differences in the influence of amino acids on water structure have been noticed. The effect of the hydrophobic side chain of an amino acid on the solvent interactions seems to be enhanced because of the specific cooperative coupling of water strong H-bond chain, connecting the carboxyl and amino groups, with the clathrate-like H-bond network surrounding the hydrocarbon side chain. The parameter derived from the spectral data, which corresponds to the contributions of the population of weak hydrogen bonds of water molecules which have been substituted by the stronger ones in the hydration sphere of amino acids, correlated well with the amino acid hydrophobicity indexes.

Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

PubMed Central

Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

2015-01-01

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism. PMID:25588215

Acetic acid can catalyze succinimide formation from aspartic acid residues by a concerted bond reorganization mechanism: a computational study.

PubMed

Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

2015-01-12

Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four vλ6 proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wall, J.S.; Gupta, V.; Wilkerson, M.

2004-04-01

Primary (AL) amyloidosis results from the pathologic deposition of monoclonal light chains as amyloid fibrils. Studies of recombinant-derived variable region (V{sub L}) fragments of these proteins have shown an inverse relationship between thermodynamic stability and fibrillogenic potential. Further, ionic interactions within the V{sub L} domain were predicted to influence the kinetics of light chain fibrillogenicity, as evidenced from our analyses of a relatively stable V{sub {lambda}}6 protein (Jto) with a long range electrostatic interaction between Asp and Arg side chains at position 29 and 68, respectively, and an unstable, highly fibrillogenic V{sub {lambda}}6 protein (Wil) that had neutral amino acidsmore » at these locations. To test this hypothesis, we have generated two Jto-related mutants designed to disrupt the interaction between Asp 29 and Arg 68 (JtoD29A and JtoR68S). Although the thermodynamic stabilities of unfolding for these two molecules were identical, they exhibited very different kinetics of fibril formation: the rate of JtoD29A fibrillogenesis was slow and comparable to the parent molecule, whereas that of JtoR68S was significantly faster. High-resolution X-ray diffraction analyses of crystals prepared from the two mutants having the same space group and unit cell dimensions revealed no significant main-chain conformational changes. However, several notable side-chain alterations were observed in JtoR68S, as compared with JtoD29A, that resulted in the solvent exposure of a greater hydrophobic surface and modifications in the electrostatic potential surface. We posit that these differences contributed to the enhanced fibrillogenic potential of the Arg 68 mutant, since both Jto mutants lacked the intrachain ionic interaction and were equivalently unstable. The information gleaned from our studies has provided insight into structural parameters that in addition to overall thermodynamic stability, contribute to the fibril forming propensity of immunoglobulin light chains.« less