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.

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.

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.

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.

DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes

PubMed Central

Kleiner, Ralph E.; Brudno, Yevgeny; Birnbaum, Michael E.; Liu, David R.

2009-01-01

The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that the polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence-specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry, but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step towards the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each

Assessing the influence of side-chain and main-chain aromatic benzyltrimethyl ammonium on anion exchange membranes.

PubMed

Li, Xiuhua; Nie, Guanghui; Tao, Jinxiong; Wu, Wenjun; Wang, Liuchan; Liao, Shijun

2014-05-28

3,3'-Di(4″-methyl-phenyl)-4,4'-difluorodiphenyl sulfone (DMPDFPS), a new monomer with two pendent benzyl groups, was easily prepared by Suzuki coupling reaction in high yield. A series of side-chain type ionomers (PAES-Qs) containing pendant side-chain benzyltrimethylammonium groups, which linked to the backbone by alkaline resisting conjugated C-C bonds, were synthesized via polycondensation, bromination, followed by quaternization and alkalization. To assess the influence of side-chain and main-chain aromatic benzyltrimethylammonium on anion exchange membranes (AEMs), the main-chain type ionomers (MPAES-Qs) with the same backbone were synthesized following the similar procedure. GPC and (1)H NMR results indicate that the bromination shows no reaction selectivity of polymer configurations and ionizations of the side-chain type polymers display higher conversions than that of the main-chain type ones do. These two kinds of AEMs were evaluated in terms of ion exchange capacity (IEC), water uptake, swelling ratio, λ, volumetric ion exchange capacity (IECVwet), hydroxide conductivity, mechanical and thermal properties, and chemical stability, respectively. The side-chain type structure endows AEMs with lower water uptake, swelling ratio and λ, higher IECVwet, much higher hydroxide conductivity, more robust dimensional stability, mechanical and thermal properties, and higher stability in hot alkaline solution. The side-chain type cationic groups containing molecular configurations have the distinction of being practical AEMs and membrane electrode assemblies of AEMFCs.

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.

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

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

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.

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

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

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.

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

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.

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.

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

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

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.

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.

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.

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.

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.

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

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.

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).

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.

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

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

Product ion tandem mass spectrometric differentiation of regioisomeric side-chain groups in cathinone derivatives.

PubMed

Abiedalla, Younis; DeRuiter, Jack; Clark, C Randall

2016-07-30

Precursor materials are available to prepare aminoketone drugs containing regioisomeric propyl and isopropyl side-chain groups related to the drug alpha-pyrrovalerone (Flakka) and MDPV (3,4-methylenedioxypyrrovalerone). These compounds yield equivalent regioisomeric iminium cation base peaks in electron ionization mass spectrometry (EI-MS). The propyl and isopropyl side-chain groups related to alpha-pyrrovalerone and MDPV were prepared and evaluated in EI-MS and tandem mass spectrometry (MS/MS) product ion experiments. Deuterium labeling in both the pyrrolidine and alkyl side-chain groups allowed for the confirmation of the structures for the major product ions formed from the regioisomeric EI-MS iminium cation base peaks. These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the side-chain propyl and isopropyl groups in the structure. The n-propyl side chain containing iminium cation base peak (m/z 126) in the EI-MS spectrum yields a major product ion at m/z 84 while the regioisomeric m/z 126 base peak for the isopropyl side chain yields a characteristic product ion at m/z 70. Deuterium labeling in both the pyrrolidine ring and the alkyl side chain confirmed the process for the formation of these major product ions. Product ion fragmentation provides useful data for differentiation of n-propyl and isopropyl side-chain iminium cations from cathinone derivative drugs of abuse. Regioisomeric n-propyl and isopropyl iminium cations of equal mass yield characteristic product ions identifying the alkyl side-chain regioisomers in the pyrrolidine cathinone derivatives. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

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.

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

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.

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.

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.

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.

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.

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

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

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

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

17. SOUTHEAST VIEW OF THE TAPPING SIDE OF BASIC OXYGEN ...

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

17. SOUTHEAST VIEW OF THE TAPPING SIDE OF BASIC OXYGEN FURNACE No. 2 ON THE OPERATING FLOOR OF THE FURNACE AISLE IN THE BOP SHOP. - U.S. Steel Duquesne Works, Basic Oxygen Steelmaking Plant, Along Monongahela River, Duquesne, Allegheny County, PA

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

Spectroscopy of PAHs with carbon side chains

NASA Astrophysics Data System (ADS)

Rouille, G.; Steglich, M.; Carpentier, Y.; Huisken, F.; Henning, T.

2011-05-01

The presence of polycyclic aromatic hydrocarbons (PAHs) in space has been inferred ever since sp ecific infrared emission bands were interpreted as their collective fingerprint. In parallel, it has been admitted that the famous diffuse interstellar bands (DIBs), which are absorption features observed in the visible wavelength range, are bands belonging to the electronic spectra of free-flying interstellar molecules yet to be identified. As neutral PAHs of medium and large sizes exhibit absorption bands in the range where the DIBs are found, these molecules, which also fulfill other criteria, have been proposed as potential carriers. Studies of small PAHs in solutions have shown that adding an ethynyl side chain (--CCH) to their structure causes their electronic transitions to shift toward longer wavelengths. This fact, added to the observations of interstellar polyynyl radicals, motivated our current research project on PAHs carrying polyynyl side chains. In a first stage, we are measuring the electronic spectra of small PAHs and of their ethynyl and butadiynyl (--CCCCH) derivatives at cryogenic temperatures in rare gas matrices. Then, measurements will be carried out in supersonic jets, providing us with spectra obtained under conditions relevant to the study of free-flying interstellar molecules. The results of IR absorption measurements will be included in our set of new data. As a complement to our laboratory study on the substituted PAHs, quantum chemical calculations are carried out to interprete and simulate their IR and vibronic spectra. We use the density functional theory approach and its time-dependent extension for calculating the electronic ground states and the electronically excited states, respectively. Through the analysis of the new data, it will be determined whether PAHs carrying polyynyl side chains can play a role in interstellar phenomena. The latest results of this on-going project will be presented.

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.

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

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

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

NASA Astrophysics Data System (ADS)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

Rapid and scalable synthesis of innovative unnatural α,β or γ-amino acids functionalized with tertiary amines on their side-chains.

PubMed

Schneider, Séverine; Ftouni, Hussein; Niu, Songlin; Schmitt, Martine; Simonin, Frédéric; Bihel, Frédéric

2015-07-07

We report a selective ruthenium catalyzed reduction of tertiary amides on the side chain of Fmoc-Gln-OtBu derivatives, leading to innovative unnatural α,β or γ-amino acids functionalized with tertiary amines. Rapid and scalable, this process allowed us to build a library of basic unnatural amino acids at the gram-scale and directly usable for liquid- or solid-phase peptide synthesis. The diversity of available tertiary amines allows us to modulate the physicochemical properties of the resulting amino acids, such as basicity or hydrophobicity.

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

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.

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

PubMed Central

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-01-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD. PMID:26899474

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

NASA Astrophysics Data System (ADS)

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-02-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

Modified melanocortin tetrapeptide Ac-His-dPhe-Arg-Trp-NH at the arginine side chain with ureas and thioureas.

PubMed

Joseph, C G; Sorensen, N B; Wood, M S; Xiang, Z; Moore, M C; Haskell-Luevano, C

2005-11-01

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

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.

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.

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

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

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

Modification of Side Chains of Conjugated Molecules and Polymers for Charge Mobility Enhancement and Sensing Functionality.

PubMed

Liu, Zitong; Zhang, Guanxin; Zhang, Deqing

2018-06-19

Organic semiconductors have received increasing attentions in recent years because of their promising applications in various optoelectronic devices. The key performance metric for organic semiconductors is charge carrier mobility, which is governed by the electronic structures of conjugated backbones and intermolecular/interchain π-π interactions and packing in both microscopic and macroscopic levels. For this reason, more efforts have been paid to the design and synthesis of conjugated frameworks for organic semiconductors with high charge mobilities. However, recent studies manifest that appropriate modifications of side chains that are linked to conjugated frameworks can improve the intermolecular/interchain packing order and boost charge mobilities. In this Account, we discuss our research results in context of modification of side chains in organic semiconductors for charge mobility enhancement. These include the following: (i) The lengths of alkyl chains in sulfur-rich thiepin-fused heteroacences can dramatically influence the intermolecular arrangements and orbital overlaps, ushering in different hole mobilities. Inversely, the lamellar stacking modes of alkyl chains in naphthalene diimide (NDI) derivatives with tetrathiafulvalene (TTF) units are affected by the structures of conjugated cores. (ii) The steric hindrances owing to the bulky branching chains can be weakened by partial replacement of the branching alkyl chains with linear ones for diketopyrrolopyrrole (DPP)-based D (donor)-A (acceptor) conjugated polymers. Such modification of side chains makes the polymer backbones more planar and thus interchain packing order and charge mobilities are improved. The incorporation of hydrophilic tri(ethylene glycol) (TEG) chains into the polymers also leads to improved interchain packing order. In particular, the polymer in which TEG side chains are distributed uniformly exhibits relatively high charge mobility without thermal annealing. (iii) The

IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank

PubMed Central

Nadzirin, Nurul; Willett, Peter; Artymiuk, Peter J.; Firdaus-Raih, Mohd

2013-01-01

We describe a server that allows the interrogation of the Protein Data Bank for hypothetical 3D side chain patterns that are not limited to known patterns from existing 3D structures. A minimal side chain description allows a variety of side chain orientations to exist within the pattern, and generic side chain types such as acid, base and hydroxyl-containing can be additionally deployed in the search query. Moreover, only a subset of distances between the side chains need be specified. We illustrate these capabilities in case studies involving arginine stacks, serine-acid group arrangements and multiple catalytic triad-like configurations. The IMAAAGINE server can be accessed at http://mfrlab.org/grafss/imaaagine/. PMID:23716645

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.

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

Actinobacterial Acyl Coenzyme A Synthetases Involved in Steroid Side-Chain Catabolism

PubMed Central

Casabon, Israël; Swain, Kendra; Crowe, Adam M.

2014-01-01

Bacterial steroid catabolism is an important component of the global carbon cycle and has applications in drug synthesis. Pathways for this catabolism involve multiple acyl coenzyme A (CoA) synthetases, which activate alkanoate substituents for β-oxidation. The functions of these synthetases are poorly understood. We enzymatically characterized four distinct acyl-CoA synthetases from the cholate catabolic pathway of Rhodococcus jostii RHA1 and the cholesterol catabolic pathway of Mycobacterium tuberculosis. Phylogenetic analysis of 70 acyl-CoA synthetases predicted to be involved in steroid metabolism revealed that the characterized synthetases each represent an orthologous class with a distinct function in steroid side-chain degradation. The synthetases were specific for the length of alkanoate substituent. FadD19 from M. tuberculosis H37Rv (FadD19Mtb) transformed 3-oxo-4-cholesten-26-oate (kcat/Km = 0.33 × 105 ± 0.03 × 105 M−1 s−1) and represents orthologs that activate the C8 side chain of cholesterol. Both CasGRHA1 and FadD17Mtb are steroid-24-oyl-CoA synthetases. CasG and its orthologs activate the C5 side chain of cholate, while FadD17 and its orthologs appear to activate the C5 side chain of one or more cholesterol metabolites. CasIRHA1 is a steroid-22-oyl-CoA synthetase, representing orthologs that activate metabolites with a C3 side chain, which accumulate during cholate catabolism. CasI had similar apparent specificities for substrates with intact or extensively degraded steroid nuclei, exemplified by 3-oxo-23,24-bisnorchol-4-en-22-oate and 1β(2′-propanoate)-3aα-H-4α(3″-propanoate)-7aβ-methylhexahydro-5-indanone (kcat/Km = 2.4 × 105 ± 0.1 × 105 M−1 s−1 and 3.2 × 105 ± 0.3 × 105 M−1 s−1, respectively). Acyl-CoA synthetase classes involved in cholate catabolism were found in both Actinobacteria and Proteobacteria. Overall, this study provides insight into the physiological roles of acyl-CoA synthetases in steroid catabolism and

Quantitative Profiling of Feruloylated Arabinoxylan Side-Chains from Graminaceous Cell Walls

PubMed Central

Schendel, Rachel R.; Meyer, Marleen R.; Bunzel, Mirko

2016-01-01

Graminaceous arabinoxylans are distinguished by decoration with feruloylated monosaccharidic and oligosaccharidic side-chains. Although it is hypothesized that structural complexity and abundance of these feruloylated arabinoxylan side-chains may contribute, among other factors, to resistance of plant cell walls to enzymatic degradation, quantitative profiling approaches for these structural units in plant cell wall materials have not been described yet. Here we report the development and application of a rapid and robust method enabling the quantitative comparison of feruloylated side-chain profiles in cell wall materials following mildly acidic hydrolysis, C18-solid phase extraction (SPE), reduction under aprotic conditions, and liquid chromatography with diode-array detection/mass spectrometry (LC-DAD/MS) separation and detection. The method was applied to the insoluble fiber/cell wall materials isolated from 12 whole grains: wild rice (Zizania aquatica L.), long-grain brown rice (Oryza sativa L.), rye (Secale cereale L.), kamut (Triticum turanicum Jakubz.), wheat (Triticum aestivum L.), spelt (Triticum spelta L.), intermediate wheatgrass (Thinopyrum intermedium), maize (Zea mays L.), popcorn (Zea mays L. var. everta), oat (Avena sativa L.) (dehulled), barley (Hordeum vulgare L.) (dehulled), and proso millet (Panicum miliaceum L.). Between 51 and 96% of the total esterified monomeric ferulates were represented in the quantified compounds captured in the feruloylated side-chain profiles, which confirms the significance of these structures to the global arabinoxylan structure in terms of quantity. The method provided new structural insights into cereal grain arabinoxylans, in particular, that the structural moiety α-l-galactopyranosyl-(1→2)-β-d-xylopyranosyl-(1→2)-5-O-trans-feruloyl-l-arabinofuranose (FAXG), which had previously only been described in maize, is ubiquitous to cereal grains. PMID:26834763

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.

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

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

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

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.

Side chain engineering of poly-thiophene and its impact on crystalline silicon based hybrid solar cells

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

Zellmeier, M.; Rappich, J.; Nickel, N. H.

The influence of ether groups in the side chain of spin coated regioregular polythiophene derivatives on the polymer layer formation and the hybrid solar cell properties was investigated using electrical, optical, and X-ray diffraction experiments. The polymer layers are of high crystallinity but the polymer with 3 ether groups in the side chain (P3TOT) did not show any vibrational fine structure in the UV-Vis spectrum. The presence of ether groups in the side chains leads to better adhesion resulting in thinner and more homogeneous polymer layers. This, in turn, enhances the electronic properties of the planar c-Si/poly-thiophene hybrid solar cell.more » We find that the power conversion efficiency increases with the number of ether groups in the side chains, and a maximum power conversion efficiency of η = 9.6% is achieved even in simple planar structures.« less

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.

Topological side-chain classification of beta-turns: ideal motifs for peptidomimetic development.

PubMed

Tran, Tran Trung; McKie, Jim; Meutermans, Wim D F; Bourne, Gregory T; Andrews, Peter R; Smythe, Mark L

2005-08-01

Beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. Beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi2, psi2, phi3 and psi3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C(alpha)-C(beta) vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C(alpha)-C(beta) vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

Fitmunk: improving protein structures by accurate, automatic modeling of side-chain conformations.

PubMed

Porebski, Przemyslaw Jerzy; Cymborowski, Marcin; Pasenkiewicz-Gierula, Marta; Minor, Wladek

2016-02-01

Improvements in crystallographic hardware and software have allowed automated structure-solution pipelines to approach a near-`one-click' experience for the initial determination of macromolecular structures. However, in many cases the resulting initial model requires a laborious, iterative process of refinement and validation. A new method has been developed for the automatic modeling of side-chain conformations that takes advantage of rotamer-prediction methods in a crystallographic context. The algorithm, which is based on deterministic dead-end elimination (DEE) theory, uses new dense conformer libraries and a hybrid energy function derived from experimental data and prior information about rotamer frequencies to find the optimal conformation of each side chain. In contrast to existing methods, which incorporate the electron-density term into protein-modeling frameworks, the proposed algorithm is designed to take advantage of the highly discriminatory nature of electron-density maps. This method has been implemented in the program Fitmunk, which uses extensive conformational sampling. This improves the accuracy of the modeling and makes it a versatile tool for crystallographic model building, refinement and validation. Fitmunk was extensively tested on over 115 new structures, as well as a subset of 1100 structures from the PDB. It is demonstrated that the ability of Fitmunk to model more than 95% of side chains accurately is beneficial for improving the quality of crystallographic protein models, especially at medium and low resolutions. Fitmunk can be used for model validation of existing structures and as a tool to assess whether side chains are modeled optimally or could be better fitted into electron density. Fitmunk is available as a web service at http://kniahini.med.virginia.edu/fitmunk/server/ or at http://fitmunk.bitbucket.org/.

Paired basic science and clinical problem-based learning faculty teaching side by side: do students evaluate them differently?

PubMed

Stevenson, Frazier T; Bowe, Connie M; Gandour-Edwards, Regina; Kumari, Vijaya G

2005-02-01

Many studies have evaluated the desirability of expert versus non-expert facilitators in problem-based learning (PBL), but performance differences between basic science and clinical facilitators has been less studied. In a PBL course at our university, pairs of faculty facilitators (1 clinician, 1 basic scientist) were assigned to student groups to maximise integration of basic science with clinical science. This study set out to establish whether students evaluate basic science and clinical faculty members differently when they teach side by side. Online questionnaires were used to survey 188 students about their faculty facilitators immediately after they completed each of 3 serial PBL cases. Overall satisfaction was measured using a scale of 1-7 and yes/no responses were gathered from closed questions describing faculty performance. results: Year 1 students rated basic science and clinical facilitators the same, but Year 2 students rated the clinicians higher overall. Year 1 students rated basic scientists higher in their ability to understand the limits of their own knowledge. Year 2 students rated the clinicians higher in several content expertise-linked areas: preparedness, promotion of in-depth understanding, and ability to focus the group, and down-rated the basic scientists for demonstrating overspecialised knowledge. Students' overall ratings of individual faculty best correlated with the qualities of stimulation, focus and preparedness, but not with overspecialisation, excessive interjection of the faculty member's own opinions, and encouragement of psychosocial issue discussion. When taught by paired basic science and clinical PBL facilitators, students in Year 1 rated basic science and clinical PBL faculty equally, while Year 2 students rated clinicians more highly overall. The Year 2 difference may be explained by perceived differences in content expertise.

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

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.

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.

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.

Clusters of isoleucine, leucine, and valine side chains define cores of stability in high-energy states of globular proteins: Sequence determinants of structure and stability.

PubMed

Kathuria, Sagar V; Chan, Yvonne H; Nobrega, R Paul; Özen, Ayşegül; Matthews, C Robert

2016-03-01

Measurements of protection against exchange of main chain amide hydrogens (NH) with solvent hydrogens in globular proteins have provided remarkable insights into the structures of rare high-energy states that populate their folding free-energy surfaces. Lacking, however, has been a unifying theory that rationalizes these high-energy states in terms of the structures and sequences of their resident proteins. The Branched Aliphatic Side Chain (BASiC) hypothesis has been developed to explain the observed patterns of protection in a pair of TIM barrel proteins. This hypothesis supposes that the side chains of isoleucine, leucine, and valine (ILV) residues often form large hydrophobic clusters that very effectively impede the penetration of water to their underlying hydrogen bond networks and, thereby, enhance the protection against solvent exchange. The linkage between the secondary and tertiary structures enables these ILV clusters to serve as cores of stability in high-energy partially folded states. Statistically significant correlations between the locations of large ILV clusters in native conformations and strong protection against exchange for a variety of motifs reported in the literature support the generality of the BASiC hypothesis. The results also illustrate the necessity to elaborate this simple hypothesis to account for the roles of adjacent hydrocarbon moieties in defining stability cores of partially folded states along folding reaction coordinates. © 2015 The Protein Society.

Controlling the mode of operation of organic transistors through side-chain engineering.

PubMed

Giovannitti, Alexander; Sbircea, Dan-Tiberiu; Inal, Sahika; Nielsen, Christian B; Bandiello, Enrico; Hanifi, David A; Sessolo, Michele; Malliaras, George G; McCulloch, Iain; Rivnay, Jonathan

2016-10-25

Electrolyte-gated organic transistors offer low bias operation facilitated by direct contact of the transistor channel with an electrolyte. Their operation mode is generally defined by the dimensionality of charge transport, where a field-effect transistor allows for electrostatic charge accumulation at the electrolyte/semiconductor interface, whereas an organic electrochemical transistor (OECT) facilitates penetration of ions into the bulk of the channel, considered a slow process, leading to volumetric doping and electronic transport. Conducting polymer OECTs allow for fast switching and high currents through incorporation of excess, hygroscopic ionic phases, but operate in depletion mode. Here, we show that the use of glycolated side chains on a thiophene backbone can result in accumulation mode OECTs with high currents, transconductance, and sharp subthreshold switching, while maintaining fast switching speeds. Compared with alkylated analogs of the same backbone, the triethylene glycol side chains shift the mode of operation of aqueous electrolyte-gated transistors from interfacial to bulk doping/transport and show complete and reversible electrochromism and high volumetric capacitance at low operating biases. We propose that the glycol side chains facilitate hydration and ion penetration, without compromising electronic mobility, and suggest that this synthetic approach can be used to guide the design of organic mixed conductors.

Controlling the mode of operation of organic transistors through side-chain engineering

PubMed Central

Giovannitti, Alexander; Sbircea, Dan-Tiberiu; Inal, Sahika; Nielsen, Christian B.; Bandiello, Enrico; Hanifi, David A.; Sessolo, Michele; Malliaras, George G.; McCulloch, Iain; Rivnay, Jonathan

2016-01-01

Electrolyte-gated organic transistors offer low bias operation facilitated by direct contact of the transistor channel with an electrolyte. Their operation mode is generally defined by the dimensionality of charge transport, where a field-effect transistor allows for electrostatic charge accumulation at the electrolyte/semiconductor interface, whereas an organic electrochemical transistor (OECT) facilitates penetration of ions into the bulk of the channel, considered a slow process, leading to volumetric doping and electronic transport. Conducting polymer OECTs allow for fast switching and high currents through incorporation of excess, hygroscopic ionic phases, but operate in depletion mode. Here, we show that the use of glycolated side chains on a thiophene backbone can result in accumulation mode OECTs with high currents, transconductance, and sharp subthreshold switching, while maintaining fast switching speeds. Compared with alkylated analogs of the same backbone, the triethylene glycol side chains shift the mode of operation of aqueous electrolyte-gated transistors from interfacial to bulk doping/transport and show complete and reversible electrochromism and high volumetric capacitance at low operating biases. We propose that the glycol side chains facilitate hydration and ion penetration, without compromising electronic mobility, and suggest that this synthetic approach can be used to guide the design of organic mixed conductors. PMID:27790983

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

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.

Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

PubMed

Gaines, J C; Acebes, S; Virrueta, A; Butler, M; Regan, L; O'Hern, C S

2018-05-01

We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins. © 2018 Wiley Periodicals, Inc.

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.

Accessibility of Nitroxide Side Chains: Absolute Heisenberg Exchange Rates from Power Saturation EPR

PubMed Central

Altenbach, Christian; Froncisz, Wojciech; Hemker, Roy; Mchaourab, Hassane; Hubbell, Wayne L.

2005-01-01

In site-directed spin labeling, the relative solvent accessibility of spin-labeled side chains is taken to be proportional to the Heisenberg exchange rate (Wex) of the nitroxide with a paramagnetic reagent in solution. In turn, relative values of Wex are determined by continuous wave power saturation methods and expressed as a proportional and dimensionless parameter Π. In the experiments presented here, NiEDDA is characterized as a paramagnetic reagent for solvent accessibility studies, and it is shown that absolute values of Wex can be determined from Π, and that the proportionality constant relating them is independent of the paramagnetic reagent and mobility of the nitroxide. Based on absolute exchange rates, an accessibility factor is defined (0 < ρ < 1) that serves as a quantitative measure of side-chain solvent accessibility. The accessibility factors for a nitroxide side chain at 14 different sites in T4 lysozyme are shown to correlate with a structure-based accessibility parameter derived from the crystal structure of the protein. These results provide a useful means for relating crystallographic and site-directed spin labeling data, and hence comparing crystal and solution structures. PMID:15994891

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

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.

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

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.

Microscopic theory of light-induced deformation in amorphous side-chain azobenzene polymers.

PubMed

Toshchevikov, V; Saphiannikova, M; Heinrich, G

2009-04-16

We propose a microscopic theory of light-induced deformation of side-chain azobenzene polymers taking into account the internal structure of polymer chains. Our theory is based on the fact that interaction of chromophores with the polarized light leads to the orientation anisotropy of azobenzene macromolecules which is accompanied by the appearance of mechanical stress. It is the first microscopic theory which provides the value of the light-induced stress larger than the yield stress. This result explains a possibility for the inscription of surface relief gratings in glassy side-chain azobenzene polymers. For some chemical architectures, elongation of a sample demonstrates a nonmonotonic behavior with the light intensity and can change its sign (a stretched sample starts to be uniaxially compressed), in agreement with experiments. Using a viscoplastic approach, we show that the irreversible strain of a sample, which remains after the light is switched off, decreases with increasing temperature and can disappear at certain temperature below the glass transition temperature. This theoretical prediction is also confirmed by recent experiments.

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.

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.

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.

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.

Conjugation of diisocyanate side chains to dimethacrylate reduces polymerization shrinkage and increases the hardness of composite resins.

PubMed

Jan, Yih-Dean; Lee, Bor-Shiunn; Lin, Chun-Pin; Tseng, Wan-Yu

2014-04-01

Polymerization shrinkage is one of the main causes of dental restoration failure. This study tried to conjugate two diisocyanate side chains to dimethacrylate resins in order to reduce polymerization shrinkage and increase the hardness of composite resins. Diisocyanate, 2-hydroxyethyl methacrylate, and bisphenol A dimethacrylate were reacted in different ratios to form urethane-modified new resin matrices, and then mixed with 50 wt.% silica fillers. The viscosities of matrices, polymerization shrinkage, surface hardness, and degrees of conversion of experimental composite resins were then evaluated and compared with a non-modified control group. The viscosities of resin matrices increased with increasing diisocyanate side chain density. Polymerization shrinkage and degree of conversion, however, decreased with increasing diisocyanate side chain density. The surface hardness of all diisocyanate-modified groups was equal to or significantly higher than that of the control group. Conjugation of diisocyanate side chains to dimethacrylate represents an effective means of reducing polymerization shrinkage and increasing the surface hardness of dental composite resins. Copyright © 2012. Published by Elsevier B.V.

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

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.

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.

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.

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.

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.

Improved side-chain torsion potentials for the Amber ff99SB protein force field

PubMed Central

Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim; Maragakis, Paul; Klepeis, John L; Dror, Ron O; Shaw, David E

2010-01-01

Recent advances in hardware and software have enabled increasingly long molecular dynamics (MD) simulations of biomolecules, exposing certain limitations in the accuracy of the force fields used for such simulations and spurring efforts to refine these force fields. Recent modifications to the Amber and CHARMM protein force fields, for example, have improved the backbone torsion potentials, remedying deficiencies in earlier versions. Here, we further advance simulation accuracy by improving the amino acid side-chain torsion potentials of the Amber ff99SB force field. First, we used simulations of model alpha-helical systems to identify the four residue types whose rotamer distribution differed the most from expectations based on Protein Data Bank statistics. Second, we optimized the side-chain torsion potentials of these residues to match new, high-level quantum-mechanical calculations. Finally, we used microsecond-timescale MD simulations in explicit solvent to validate the resulting force field against a large set of experimental NMR measurements that directly probe side-chain conformations. The new force field, which we have termed Amber ff99SB-ILDN, exhibits considerably better agreement with the NMR data. Proteins 2010. © 2010 Wiley-Liss, Inc. PMID:20408171

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.

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

Correlation between protein secondary structure, backbone bond angles, and side-chain orientations.

PubMed

Lundgren, Martin; Niemi, Antti J

2012-08-01

We investigate the fine structure of the sp3 hybridized covalent bond geometry that governs the tetrahedral architecture around the central C(α) carbon of a protein backbone, and for this we develop new visualization techniques to analyze high-resolution x-ray structures in the Protein Data Bank. We observe that there is a correlation between the deformations of the ideal tetrahedral symmetry and the local secondary structure of the protein. We propose a universal coarse-grained energy function to describe the ensuing side-chain geometry in terms of the C(β) carbon orientations. The energy function can model the side-chain geometry with a subatomic precision. As an example we construct the C(α)-C(β) structure of HP35 chicken villin headpiece. We obtain a configuration that deviates less than 0.4 Å in root-mean-square distance from the experimental x-ray structure.

Evidence for in vitro binding of pectin side chains to cellulose.

PubMed

Zykwinska, Agata W; Ralet, Marie-Christine J; Garnier, Catherine D; Thibault, Jean-François J

2005-09-01

Pectins of varying structures were tested for their ability to interact with cellulose in comparison to the well-known adsorption of xyloglucan. Our results reveal that sugar beet (Beta vulgaris) and potato (Solanum tuberosum) pectins, which are rich in neutral sugar side chains, can bind in vitro to cellulose. The extent of binding varies with respect to the nature and structure of the side chains. Additionally, branched arabinans (Br-Arabinans) or debranched arabinans (Deb-Arabinans; isolated from sugar beet) and galactans (isolated from potato) were shown bind to cellulose microfibrils. The adsorption of Br-Arabinan and galactan was lower than that of Deb-Arabinan. The maximum adsorption affinity of Deb-Arabinan to cellulose was comparable to that of xyloglucan. The study of sugar beet and potato alkali-treated cell walls supports the hypothesis of pectin-cellulose interaction. Natural composites enriched in arabinans or galactans and cellulose were recovered. The binding of pectins to cellulose microfibrils may be of considerable significance in the modeling of primary cell walls of plants as well as in the process of cell wall assembly.

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.

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

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.

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.

Accelerated cell sheet detachment by copolymerizing hydrophilic PEG side chains into PNIPAm nanocomposite hydrogels.

PubMed

Liu, Dan; Wang, Tao; Liu, Xinxing; Tong, Zhen

2012-10-01

One-end-connected short poly(ethylene glycol) (PEG) side chains were facilely introduced into the poly(N-isopropylacrylamide) (PNIPAm) nanocomposite hydrogel (NC gel) via in situ copolymerization of NIPAm monomer and PEG macromonomer in the aqueous suspension of hectorite clay Laponite XLS. The NC gels were characterized with Fourier transform infrared and x-ray photoelectron spectroscopy for the composition, DSC and transmittance for the phase separation temperature, dynamic mechanical spectra and swelling ratio for the interaction. Increasing the PEG content led to a small increase in the storage modulus and the lower critical solution temperature (LCST) of the copolymerized NC gels, and the LCST of the copolymerized NC gels was still below 37 °C. The L929 cell adhesion and proliferation on the surface of these NC gels were not suppressed by the incorporation of hydrophilic PEG side chains. By lowering temperature below the LCST, the cell sheet spontaneously detached from the copolymerized NC gels. The surface morphology and surface wettability of the NC gels were detected by atom force microscope and contact angle measurement. A rough and hydrophilic surface induced by a small amount of PEG side chains was found to be favorable to accelerate the cell sheet detachment, probably due to the enhanced water permeation into the gel-cell sheet interface.

Improved modeling of side-chain--base interactions and plasticity in protein--DNA interface design.

PubMed

Thyme, Summer B; Baker, David; Bradley, Philip

2012-06-08

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed "motifs") was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein-DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. Published by Elsevier Ltd.

Predicting side-chain conformations of methionine using a hard-sphere model with stereochemical constraints

NASA Astrophysics Data System (ADS)

Virrueta, A.; Gaines, J.; O'Hern, C. S.; Regan, L.

2015-03-01

Current research in the O'Hern and Regan laboratories focuses on the development of hard-sphere models with stereochemical constraints for protein structure prediction as an alternative to molecular dynamics methods that utilize knowledge-based corrections in their force-fields. Beginning with simple hydrophobic dipeptides like valine, leucine, and isoleucine, we have shown that our model is able to reproduce the side-chain dihedral angle distributions derived from sets of high-resolution protein crystal structures. However, methionine remains an exception - our model yields a chi-3 side-chain dihedral angle distribution that is relatively uniform from 60 to 300 degrees, while the observed distribution displays peaks at 60, 180, and 300 degrees. Our goal is to resolve this discrepancy by considering clashes with neighboring residues, and averaging the reduced distribution of allowable methionine structures taken from a set of crystallized proteins. We will also re-evaluate the electron density maps from which these protein structures are derived to ensure that the methionines and their local environments are correctly modeled. This work will ultimately serve as a tool for computing side-chain entropy and protein stability. A. V. is supported by an NSF Graduate Research Fellowship and a Ford Foundation Fellowship. J. G. is supported by NIH training Grant NIH-5T15LM007056-28.

Improving proton conduction pathways in di- and triblock copolymer membranes: Branched versus linear side chains

NASA Astrophysics Data System (ADS)

Dorenbos, G.

2017-06-01

Phase separation within a series of polymer membranes in the presence of water is studied by dissipative particle dynamics. Each polymer contains hydrophobic A beads and hydrophilic C beads. Three parent architectures are constructed from a backbone composed of connected hydrophobic A beads to which short ([C]), long ([A3C]), or symmetrically branched A5[AC][AC] side chains spring off. Three di-block copolymer derivatives are constructed by covalently bonding an A30 block to each parent architecture. Also three tri-blocks with A15 blocks attached to both ends of each parent architecture are modeled. Monte Carlo tracer diffusion calculations through the water containing pores for 1226 morphologies reveal that water diffusion for parent architectures is slowest and diffusion through the di-blocks is fastest. Furthermore, diffusion increases with side chain length and is highest for branched side chains. This is explained by the increase of water pore size with , which is the average number of bonds that A beads are separated from a nearest C bead. Optimization of within the amphiphilic parent architecture is expected to be essential in improving proton conduction in polymer electrolyte membranes.

Dissecting the total transition state stabilization provided by amino acid side chains at orotidine 5'-monophosphate decarboxylase: a two-part substrate approach.

PubMed

Barnett, Shonoi A; Amyes, Tina L; Wood, Bryant M; Gerlt, John A; Richard, John P

2008-07-29

Kinetic analysis of decarboxylation catalyzed by S154A, Q215A, and S154A/Q215A mutant yeast orotidine 5'-monophosphate decarboxylases with orotidine 5'-monophosphate (OMP) and with a truncated nucleoside substrate (EO) activated by phosphite dianion shows (1) the side chain of Ser-154 stabilizes the transition state through interactions with the pyrimidine rings of OMP or EO, (2) the side chain of Gln-215 interacts with the phosphodianion group of OMP or with phosphite dianion, and (3) the interloop hydrogen bond between the side chains of Ser-154 and Gln-215 orients the amide side chain of Gln-215 to interact with the phosphodianion group of OMP or with phosphite dianion.

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.

Triazine-based sequence-defined polymers with side-chain diversity and backbone-backbone interaction motifs

DOE PAGES

Grate, Jay W.; Mo, Kai -For; Daily, Michael D.

2016-02-10

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H-bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. In conclusion, the synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen-bonding motifs, and willmore » thus enable new macromolecules and materials with useful functions.« less

Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone-Backbone Interaction Motifs.

PubMed

Grate, Jay W; Mo, Kai-For; Daily, Michael D

2016-03-14

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Triazine-based sequence-defined polymers with side-chain diversity and backbone-backbone interaction motifs

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

Grate, Jay W.; Mo, Kai -For; Daily, Michael D.

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H-bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. In conclusion, the synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen-bonding motifs, and willmore » thus enable new macromolecules and materials with useful functions.« less

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.

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.

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

The dominant role of side chains in supramolecular double helical organisation in synthetic tripeptides

NASA Astrophysics Data System (ADS)

Sharma, Ankita; Tiwari, Priyanka; Dutt Konar, Anita

2018-06-01

Peptide self-assembled nanostructures have attracted attention recently owing to their promising applications in diversified avenues. To validate the importance of sidechains in supramolecular architectural stabilization, herein this report describes the self-assembly propensities involving weak interactions in a series of model tripeptides Boc-Xaa-Aib-Yaa-OMe I-IV, (where Xaa = 4-F-Phe/NMeSer/Ile & Yaa = Tyr in peptide I-III respectively and Xaa = 4-F-Phe & Yaa = Ile in peptide IV) differing in terminal side chains. The solid state structural analysis reveals that tripeptide (I) displays supramolecular preference for double helical architecture. However, when slight modification has been introduced in the N-terminal side chains disfavour the double helical organisation (Peptide II and III). Indeed the peptides display sheet like ensemble within the framework. Besides replacement of C-terminal Tyr by Ile in peptide I even do not promote the architecture, emphasizing the dominant role of balance of side chains in stabilizing double helical organisation. The CD measurements, concentration dependant studies, NMR titrations and ROESY spectra are well in agreement with the solid state conformational investigation. Moreover the morphological experiments utilizing FE-SEM, support the heterogeneity present in the peptides. Thus this work may not only hold future promise in understanding the structure and function of neurodegenerative diseases but also assist in rational design of protein modification in biologically active peptides.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

PubMed

Bernstein, Rachel; Schmidt, Kierstin L; Harbury, Pehr B; Marqusee, Susan

2011-06-28

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape

PubMed Central

Bernstein, Rachel; Schmidt, Kierstin L.; Harbury, Pehr B.; Marqusee, Susan

2011-01-01

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated. PMID:21670244

Subcritical Water Hydrolysis of Peptides: Amino Acid Side-Chain Modifications

NASA Astrophysics Data System (ADS)

Powell, Thomas; Bowra, Steve; Cooper, Helen J.

2017-09-01

Previously we have shown that subcritical water may be used as an alternative to enzymatic digestion in the proteolysis of proteins for bottom-up proteomics. Subcritical water hydrolysis of proteins was shown to result in protein sequence coverages greater than or equal to that obtained following digestion with trypsin; however, the percentage of peptide spectral matches for the samples treated with trypsin were consistently greater than for those treated with subcritical water. This observation suggests that in addition to cleavage of the peptide bond, subcritical water treatment results in other hydrolysis products, possibly due to modifications of amino acid side chains. Here, a model peptide comprising all common amino acid residues (VQSIKCADFLHYMENPTWGR) and two further model peptides (VCFQYMDRGDR and VQSIKADFLHYENPTWGR) were treated with subcritical water with the aim of probing any induced amino acid side-chain modifications. The hydrolysis products were analyzed by direct infusion electrospray tandem mass spectrometry, either collision-induced dissociation or electron transfer dissociation, and liquid chromatography collision-induced dissociation tandem mass spectrometry. The results show preferential oxidation of cysteine to sulfinic and sulfonic acid, and oxidation of methionine. In the absence of cysteine and methionine, oxidation of tryptophan was observed. In addition, water loss from aspartic acid and C-terminal amidation were observed in harsher subcritical water conditions. [Figure not available: see fulltext.

Independent Metrics for Protein Backbone and Side-Chain Flexibility: Time Scales and Effects of Ligand Binding.

PubMed

Fuchs, Julian E; Waldner, Birgit J; Huber, Roland G; von Grafenstein, Susanne; Kramer, Christian; Liedl, Klaus R

2015-03-10

Conformational dynamics are central for understanding biomolecular structure and function, since biological macromolecules are inherently flexible at room temperature and in solution. Computational methods are nowadays capable of providing valuable information on the conformational ensembles of biomolecules. However, analysis tools and intuitive metrics that capture dynamic information from in silico generated structural ensembles are limited. In standard work-flows, flexibility in a conformational ensemble is represented through residue-wise root-mean-square fluctuations or B-factors following a global alignment. Consequently, these approaches relying on global alignments discard valuable information on local dynamics. Results inherently depend on global flexibility, residue size, and connectivity. In this study we present a novel approach for capturing positional fluctuations based on multiple local alignments instead of one single global alignment. The method captures local dynamics within a structural ensemble independent of residue type by splitting individual local and global degrees of freedom of protein backbone and side-chains. Dependence on residue type and size in the side-chains is removed via normalization with the B-factors of the isolated residue. As a test case, we demonstrate its application to a molecular dynamics simulation of bovine pancreatic trypsin inhibitor (BPTI) on the millisecond time scale. This allows for illustrating different time scales of backbone and side-chain flexibility. Additionally, we demonstrate the effects of ligand binding on side-chain flexibility of three serine proteases. We expect our new methodology for quantifying local flexibility to be helpful in unraveling local changes in biomolecular dynamics.

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

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.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

Effect of Pendant Side-Chain Sterics and Dipole Forces on Short Range Ordering in Random Polyelectrolytes

NASA Astrophysics Data System (ADS)

Nwosu, Chinomso; Pandey, Tara; Herring, Andrew; Coughlin, Edward; University of Massachusetts, Amherst Collaboration; Colorado School of Mines Collaboration

Backbone-to-backbone spacing in polymers is known to be dictated by the length of the pendant side-chains. Dipole forces in random polyelectrolytes lead to ionic clusters with a characteristic spacing that can be observed by SAXS. Repulsion due to side-chain sterics will compete with dipole forces driving cluster formation in random polyelectrolytes. A model study on short range order in anion exchange membranes (AEMs) of quaternized P4VP-ran-PI is presented. Quaternization of P4VP with alkyl bromides having different numbers of carbons, CnBr, introduces pendant side-chains as well as charges. X-ray scattering performed on PQ4VP-ran-PI(CnBr) show that when n <5 the dipole forces dominate leading to the formation of ionic clusters. However, when n >4, the chains remain separated due to sterics, forming a distinct backbone-to-backbone spacing morphology. For n=3, both dipole clustering and backbone spacing can coexist. Crosslinking of the isoprene units increased the coexistence window from n=3 to n=6. Impedance measurements show that a maximum conductivity of 110mS/cm was obtained for PQ4VP-ran-PI(C3Br). A discussion on short range order due to competition, or counter balancing, of steric repulsion and dipole forces will be presented. US Army MURI project (W911NF1010520).

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.

The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating

PubMed Central

Cui, Liying; Aleksandrov, Luba; Hou, Yue-Xian; Gentzsch, Martina; Chen, Jey-Hsin; Riordan, John R; Aleksandrov, Andrei A

2006-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel employing the ABC transporter structural motif. Deletion of a single residue (Phe508) in the first nucleotide-binding domain (NBD1), which occurs in most patients with cystic fibrosis, impairs both maturation and function of the protein. However, substitution of the Phe508 with small uncharged amino acids, including cysteine, is permissive for maturation. To explore the possible role of the phenylalanine aromatic side chain in channel gating we introduced a cysteine at this position in cysless CFTR, enabling its selective chemical modification by sulfhydryl reagents. Both cysless and wild-type CFTR ion channels have identical mean open times when activated by different nucleotide ligands. Moreover, both channels could be locked in an open state by introducing an ATPase inhibiting mutation (E1371S). However, the introduction of a single cysteine (F508C) prevented the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Chemical modification of cysless E1371S/F508C by sulfhydryl reagents was used to probe the role of the side chain in ion channel function. Specifically, benzyl-methanethiosulphonate modification of this variant restored the gating behaviour to that of cysless E1371S containing the wild-type phenylalanine at position 508. This provides the first direct evidence that a specific interaction of the Phe508 aromatic side chain plays a role in determining the residency time in the closed state. Thus, despite the fact that this aromatic side chain is not essential for CFTR folding, it is important in the ion channel function. PMID:16484308

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.

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.

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

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.

Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with basic amino acids and dipeptides.

PubMed

Suzuki, Tadashi; Shinoda, Mio; Osanai, Yohei; Isozaki, Tasuku

2013-08-22

Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has been investigated with transient absorption spectroscopy. With UV irradiation KP(-) gave rise to a carbanion through a decarboxylation reaction, and the carbanion easily abstracted a proton from the surrounding molecule to yield a 3-ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic amino acids were found to accelerate the proton transfer reaction whereas alanine and glycine had no effect on the reaction, revealing that these amino acids having a protonated side chain act as a proton donor. The formation quantum yield of EBPH was estimated to be fairly large by means of an actinometrical method with benzophenone, and the bimolecular reaction rate constant for the proton transfer between the carbanion and the protonated basic amino acids or the protonated dipeptides was successfully determined. It has become apparent that the bimolecular reaction rate constant for the proton transfer depended on the acid dissociation constant for the side chain of the amino acids for the first time. This reaction mechanism was interpreted by difference of the heat of reaction for each basic amino acid based on the thermodynamical consideration. These results strongly suggest that the side chain of the basic amino acid residue in protein should play an important role for photochemistry of KP in vivo.

Phenylalanyl-Glycyl-Phenylalanine Tripeptide: A Model System for Aromatic-Aromatic Side Chain Interactions in Proteins

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

Valdes, Haydee; Pluhackova, Kristyna; Hobza, Pavel

The performance of a wide range of quantum chemical calculations for the ab initio study of realistic model systems of aromatic-aromatic side chain interactions in proteins (in particular those π-π interactions occurring between adjacent residues along the protein sequence) is here assessed on the phenylalanyl-glycyl-phenylalanine (FGF) tripeptide. Energies and geometries obtained at different levels of theory are compared with CCSD(T)/CBS benchmark energies and RI-MP2/cc-pVTZ benchmark geometries, respectively. Consequently, a protocol of calculation alternative to the very expensive CCSD(T)/CBS is proposed. In addition to this, the preferred orientation of the Phe aromatic side chains is discussed and compared with previous resultsmore » on the topic.« less

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

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.

Microphase separation of comb copolymers with two different lengths of side chains

NASA Astrophysics Data System (ADS)

Aliev, M. A.; Kuzminyh, N. Yu.

2009-10-01

The phase behavior of the monodisperse AB comb copolymer melt contained the macromolecules of special architecture is discussed. Each macromolecule is assumed to be composed of two comb blocks which differ in numbers of side chains and numbers of monomer units in these chains. It is shown (by analysis of the structure factor of the melt) that microphase separation at two different length scales in the melt is possible. The large and small length scales correspond to separation between comb blocks and separation between monomer units in repeating fragments of blocks, respectively. The classification diagrams indicated which length scale is favored for a given parameters of chemical structure of macromolecules are constructed.

Modeling side-chains using molecular dynamics improve recognition of binding region in CAPRI targets.

PubMed

Camacho, Carlos J

2005-08-01

The CAPRI-II experiment added an extra level of complexity to the problem of predicting protein-protein interactions by including 5 targets for which participants had to build or complete the 3-dimensional (3D) structure of either the receptor or ligand based on the structure of a close homolog. In this article, we describe how modeling key side-chains using molecular dynamics (MD) in explicit solvent improved the recognition of the binding region of a free energy- based computational docking method. In particular, we show that MD is able to predict with relatively high accuracy the rotamer conformation of the anchor side-chains important for molecular recognition as suggested by Rajamani et al. (Proc Natl Acad Sci USA 2004;101:11287-11292). As expected, the conformations are some of the most common rotamers for the given residue, while latch side-chains that undergo induced fit upon binding are forced into less common conformations. Using these models as starting conformations in conjunction with the rigid-body docking server ClusPro and the flexible docking algorithm SmoothDock, we produced valuable predictions for 6 of the 9 targets in CAPRI-II, missing only the 3 targets that underwent significant structural rearrangements upon binding. We also show that our free energy- based scoring function, consisting of the sum of van der Waals, Coulombic electrostatic with a distance-dependent dielectric, and desolvation free energy successfully discriminates the nativelike conformation of our submitted predictions. The latter emphasizes the critical role that thermodynamics plays on our methodology, and validates the generality of the algorithm to predict protein interactions.

Fused-Ring Acceptors with Asymmetric Side Chains for High-Performance Thick-Film Organic Solar Cells.

PubMed

Feng, Shiyu; Zhang, Cai'e; Liu, Yahui; Bi, Zhaozhao; Zhang, Zhe; Xu, Xinjun; Ma, Wei; Bo, Zhishan

2017-11-01

A kind of new fused-ring electron acceptor, IDT-OB, bearing asymmetric side chains, is synthesized for high-efficiency thick-film organic solar cells. The introduction of asymmetric side chains can increase the solubility of acceptor molecules, enable the acceptor molecules to pack closely in a dislocated way, and form favorable phase separation when blended with PBDB-T. As expected, PBDB-T:IDT-OB-based devices exhibit high and balanced hole and electron mobility and give a high power conversion efficiency (PCE) of 10.12%. More importantly, the IDT-OB-based devices are not very sensitive to the film thickness, a PCE of 9.17% can still be obtained even the thickness of active layer is up to 210 nm. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

PubMed

Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

2016-09-12

Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions

Side chain flexibility and the pore dimensions in the GABAA receptor

NASA Astrophysics Data System (ADS)

Rossokhin, Alexey V.; Zhorov, Boris S.

2016-07-01

Permeation of ions through open channels and their accessibility to pore-targeting drugs depend on the pore cross-sectional dimensions, which are known only for static X-ray and cryo-EM structures. Here, we have built homology models of the closed, open and desensitized α1β2γ2 GABAA receptor (GABAAR). The models are based, respectively, on the X-ray structure of α3 glycine receptor (α3 GlyR), cryo-EM structure of α1 GlyR and X-ray structure of β3 GABAAR. We employed Monte Carlo energy minimizations to explore how the pore lumen may increase due to repulsions of flexible side chains from a variable-diameter electroneutral atom (an expanding sphere) pulled through the pore. The expanding sphere computations predicted that the pore diameter averaged along the permeation pathway is larger by approximately 3 Å than that computed for the models with fixed sidechains. Our models predict three major pore constrictions located at the levels of -2', 9' and 20' residues. Residues around the -2' and 9' rings are known to form the desensitization and activation gates of GABAAR. Our computations predict that the 20' ring may also serve as GABAAR gate whose physiological role is unclear. The side chain flexibility of residues -2', 9' and 20' and hence the dimensions of the constrictions depend on the GABAAR functional state.

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.

Influence of the side chain and substrate on polythiophene thin film surface, bulk, and buried interfacial structures.

PubMed

Xiao, Minyu; Jasensky, Joshua; Zhang, Xiaoxian; Li, Yaoxin; Pichan, Cayla; Lu, Xiaolin; Chen, Zhan

2016-08-10

The molecular structures of organic semiconducting thin films mediate the performance of various devices composed of such materials. To fully understand how the structures of organic semiconductors alter on substrates due to different polymer side chains and different interfacial interactions, thin films of two kinds of polythiophene derivatives with different side-chains, poly(3-hexylthiophene) (P3HT) and poly(3-potassium-6-hexanoate thiophene) (P3KHT), were deposited and compared on various surfaces. A combination of analytical tools was applied in this research: contact angle goniometry and X-ray photoelectron spectroscopy (XPS) were used to characterize substrate dielectric surfaces with varied hydrophobicity for polymer film deposition; X-ray diffraction and UV-vis spectroscopy were used to examine the polythiophene film bulk structure; sum frequency generation (SFG) vibrational spectroscopy was utilized to probe the molecular structures of polymer film surfaces in air and buried solid/solid interfaces. Both side-chain hydrophobicity and substrate hydrophobicity were found to mediate the crystallinity of the polythiophene film, as well as the orientation of the thiophene ring within the polymer backbone at the buried polymer/substrate interface and the polymer thin film surface in air. For the same type of polythiophene film deposited on different substrates, a more hydrophobic substrate surface induced thiophene ring alignment with the surface normal at both the buried interface and on the surface in air. For different films (P3HT vs. P3KHT) deposited on the same dielectric substrate, a more hydrophobic polythiophene side chain caused the thiophene ring to align more towards the surface at the buried polymer/substrate interface and on the surface in air. We believe that the polythiophene surface, bulk, and buried interfacial molecular structures all influence the hole mobility within the polythiophene film. Successful characterization of an organic conducting

Side Chain Engineering on Medium Bandgap Copolymers to Suppress Triplet Formation for High-Efficiency Polymer Solar Cells.

PubMed

Xue, Lingwei; Yang, Yankang; Xu, Jianqiu; Zhang, Chunfeng; Bin, Haijun; Zhang, Zhi-Guo; Qiu, Beibei; Li, Xiaojun; Sun, Chenkai; Gao, Liang; Yao, Jia; Chen, Xiaofeng; Yang, Yunxu; Xiao, Min; Li, Yongfang

2017-10-01

Suppression of carrier recombination is critically important in realizing high-efficiency polymer solar cells. Herein, it is demonstrated difluoro-substitution of thiophene conjugated side chain on donor polymer can suppress triplet formation for reducing carrier recombination. A new medium bandgap 2D-conjugated D-A copolymer J91 is designed and synthesized with bi(alkyl-difluorothienyl)-benzodithiophene as donor unit and fluorobenzotriazole as acceptor unit, for taking the advantages of the synergistic fluorination on the backbone and thiophene side chain. J91 demonstrates enhanced absorption, low-lying highest occupied molecular orbital energy level, and higher hole mobility, in comparison with its control polymer J52 without fluorination on the thiophene side chains. The transient absorption spectra indicate that J91 can suppress the triplet formation in its blend film with n-type organic semiconductor acceptor m-ITIC (3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone)-5,5,11,11-tetrakis(3-hexylphenyl)-dithieno[2,3-d:2,3'-d']-s-indaceno[1,2-b:5,6-b']-dithiophene). With these favorable properties, a higher power conversion efficiency of 11.63% with high V OC of 0.984 V and high J SC of 18.03 mA cm -2 is obtained for the polymer solar cells based on J91/m-ITIC with thermal annealing. The improved photovoltaic performance by thermal annealing is explained from the morphology change upon thermal annealing as revealed by photoinduced force microscopy. The results indicate that side chain engineering can provide a new solution to suppress carrier recombination toward high efficiency, thus deserves further attention. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polythiophene Derivative with a Side Chain Chromophore as Photovoltaic and Photorefractive Materials

DTIC Science & Technology

1993-11-17

the desired bulk property in the polymer such as water solubility,1 8 optical activity,19 ionic conductivity 20 or liquid crystalline properties. 2 1...photoexcitation, which is similar to photoinduced polarization observed in the Langmuir - Blodgett (L-B) films of donor-acceptor molecules. 23 But due to...Maximum 200 Words) A new, solution processable, thiophene copolymer with a side chain nonlinear optical (NLO) chromophore namely Poly (3-octylthiophene

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.

Characterization of an Aldolase Involved in Cholesterol Side Chain Degradation in Mycobacterium tuberculosis.

PubMed

Gilbert, Stephanie; Hood, LaChae; Seah, Stephen Y K

2018-01-15

The heteromeric acyl coenzyme A (acyl-CoA) dehydrogenase FadE28-FadE29 and the enoyl-CoA hydratase ChsH1-ChsH2, encoded by genes within the intracellular growth ( igr ) operon of Mycobacterium tuberculosis , catalyze the dehydrogenation of the cholesterol metabolite 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA), with a 3-carbon side chain, and subsequent hydration of the product 3-oxo-4,17-pregnadiene-20-carboxyl-CoA (3-OPDC-CoA) to form 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA (17-HOPC-CoA). The gene downstream of chsH2 , i.e., ltp2 , was expressed in recombinant Rhodococcus jostii RHA1 in combination with other genes within the igr operon. His-tagged Ltp2 copurified with untagged ChsH1-ChsH2, ChsH2, or the C-terminal domain of ChsH2, which contains a domain of unknown function (DUF35). Ltp2 in association with ChsH1-ChsH2 or just the DUF35 domain of ChsH2 was shown to catalyze the retroaldol cleavage of 17-HOPC-CoA to form androst-4-ene-3,17-dione and propionyl-CoA. Steady-state kinetic analysis using the Ltp2-DUF35 complex showed that the aldolase had optimal activity at pH 7.5, with a K m of 6.54 ± 0.90 μM and a k cat of 159 ± 8.50 s -1 ChsH1-ChsH2 could hydrate only about 30% of 3-OPDC-CoA, but this unfavorable equilibrium could be overcome when the aldolase was present to remove the hydrated product, providing a rationale for the close association of the aldolase with the hydratase. Homologs of ChsH1, ChsH2, and Ltp2 are found in steroid-degrading Gram-positive and Gram-negative bacteria, suggesting that side chains of diverse steroids may be cleaved by aldolases in the bacteria. IMPORTANCE The C-C bond cleavage of the D-ring side chain of cholesterol was shown to be catalyzed by an aldolase. The aldolase associates with the hydratase that catalyzes the preceding reaction in the cholesterol side chain degradation pathway. These enzymes are encoded by genes within the intracellular growth ( igr ) operon of M. tuberculosis , and the operon was demonstrated

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.

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.

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.

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.

Molecular origin of urea driven hydrophobic polymer collapse and unfolding depending on side chain chemistry.

PubMed

Nayar, Divya; Folberth, Angelina; van der Vegt, Nico F A

2017-07-19

Osmolytes affect hydrophobic collapse and protein folding equilibria. The underlying mechanisms are, however, not well understood. We report large-scale conformational sampling of two hydrophobic polymers with secondary and tertiary amide side chains using extensive molecular dynamics simulations. The calculated free energy of unfolding increases with urea for the secondary amide, yet decreases for the tertiary amide, in agreement with experiment. The underlying mechanism is rooted in opposing entropic driving forces: while urea screens the hydrophobic macromolecular interface and drives unfolding of the tertiary amide, urea's concomitant loss in configurational entropy drives collapse of the secondary amide. Only at sufficiently high urea concentrations bivalent urea hydrogen bonding interactions with the secondary amide lead to further stabilisation of its collapsed state. The observations provide a new angle on the interplay between side chain chemistry, urea hydrogen bonding, and the role of urea in attenuating or strengthening the hydrophobic effect.

All-acrylic multigraft copolymers: Effect of side chain molecular weight and volume fraction on mechanical behavior

DOE PAGES

Goodwin, Andrew; Wang, Weiyu; Kang, Nam -Goo; ...

2015-08-21

We present in this paper the synthesis of poly(n-butyl acrylate)-g-poly(methyl methacrylate) (PnBA-g-PMMA) multigraft copolymers via a grafting-through (macromonomer) approach. The synthesis was performed using two controlled polymerization techniques. The PMMA macromonomer was obtained by high-vacuum anionic polymerization followed by the copolymerization of n-butyl acrylate and PMMA macromonomer using reversible addition–fragmentation chain transfer (RAFT) polymerization to yield the desired all-acrylic multigraft structures. The PnBA-g-PMMA multigraft structures exhibit randomly spaced branch points with various PMMA contents, ranging from 15 to 40 vol %, allowing an investigation into how physical properties vary with differences in the number of branch points and molecular weightmore » of grafted side chains. The determination of molecular weight and polydispersity indices of both the PMMA macromonomer and the graft copolymers was carried out using size exclusion chromatography with triple detection, and the structural characteristics of both the macromonomer and PnBA-g-PMMA graft materials were characterized by 1H and 13C NMR. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was employed for monitoring the macromonomer synthesis. Thermal characteristics of the materials were analyzed using differential scanning calorimetry and thermogravimetric analysis. The mechanical performance of the graft materials was characterized by rheology and dynamic mechanical analysis, revealing that samples with PMMA content of 25–40 vol % exhibit superior elastomeric properties as compared to materials containing short PMMA side chains or <25 vol % PMMA. In conclusion, atomic force microscopy showed a varying degree of microphase separation between the glassy and rubbery components that is strongly dependent on PMMA side chain molecular weight.« less

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.

Aromatic Side Chain Water-to-Lipid Transfer Free Energies Show a Depth Dependence across the Membrane Normal.

PubMed

McDonald, Sarah K; Fleming, Karen G

2016-06-29

Quantitating and understanding the physical forces responsible for the interactions of biomolecules are fundamental to the biological sciences. This is especially challenging for membrane proteins because they are embedded within cellular bilayers that provide a unique medium in which hydrophobic sequences must fold. Knowledge of the energetics of protein-lipid interactions is thus vital to understand cellular processes involving membrane proteins. Here we used a host-guest mutational strategy to calculate the Gibbs free energy changes of water-to-lipid transfer for the aromatic side chains Trp, Tyr, and Phe as a function of depth in the membrane. This work reveals an energetic gradient in the transfer free energies for Trp and Tyr, where transfer was most favorable to the membrane interfacial region and comparatively less favorable into the bilayer center. The transfer energetics follows the concentration gradient of polar atoms across the bilayer normal that naturally occurs in biological membranes. Additional measurements revealed nearest-neighbor coupling in the data set are influenced by a network of aromatic side chains in the host protein. Taken together, these results show that aromatic side chains contribute significantly to membrane protein stability through either aromatic-aromatic interactions or placement at the membrane interface.

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.

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.

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

Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

PubMed Central

Niu, Xiaowei

2011-01-01

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger. PMID:21576375

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

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.

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.

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

Naphthalenetetracarboxylic diimide layer-based transistors with nanometer oxide and side chain dielectrics operating below one volt.

PubMed

Jung, Byung Jun; Martinez Hardigree, Josue F; Dhar, Bal Mukund; Dawidczyk, Thomas J; Sun, Jia; See, Kevin Cua; Katz, Howard E

2011-04-26

We designed a new naphthalenetetracarboxylic diimide (NTCDI) semiconductor molecule with long fluoroalkylbenzyl side chains. The side chains, 1.2 nm long, not only aid in self-assembly and kinetically stabilize injected electrons but also act as part of the gate dielectric in field-effect transistors. On Si substrates coated only with the 2 nm thick native oxide, NTCDI semiconductor films were deposited with thicknesses from 17 to 120 nm. Top contact Au electrodes were deposited as sources and drains. The devices showed good transistor characteristics in air with 0.1-1 μA of drain current at 0.5 V of V(G) and V(DS) and W/L of 10-20, even though channel width (250 μm) is over 1000 times the distance (20 nm) between gate and drain electrodes. The extracted capacitance-times-mobility product, an expression of the sheet transconductance, can exceed 100 nS V(-1), 2 orders of magnitude higher than typical organic transistors. The vertical low-frequency capacitance with gate voltage applied in the accumulation regime reached as high as 650 nF/cm(2), matching the harmonic sum of capacitances of the native oxide and one side chain and indicating that some gate-induced carriers in such devices are distributed among all of the NTCDI core layers, although the preponderance of the carriers are still near the gate electrode. Besides demonstrating and analyzing thickness-dependent NTCDI-based transistor behavior, we also showed <1 V detection of dinitrotoluene vapor by such transistors.

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.

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.

What the ultimate polymeric electro-optic materials will be: guest-host, crosslinked, or side-chain?

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Zhang, Hua; Oh, Min-Cheol; Dalton, Larry R.; Steier, William H.

2003-07-01

Material processing and device fabrication of many different electro-optic (EO) polymers developed at USC are reviewed. Detailed discussion is given to guest-host CLD/APCs, crosslinking perfluorocyclobutane (PFCB) polymer CX1, and thermally stable side-chain polymers CX2 and CX3. Excellent EO performance (1.4V at 1.31 μm, 2.1 V at 1.55 μm) was achieved in CLD/APC Mach-Zehnder modulators (2-cm, push-pull). CLD/APCs also possess low optical losses (1.2 dB/cm in slab waveguides and in thick core channel waveguides). However, the guest-host materials only have limited thermal stability (110-132 °C in short term, <60 °C in long term) and require special techniques in device fabrication. The crosslinking polymer CX1 was able to provide long-term stability at 85 oC when fully cured. It also has a low optical loss (comparable to CLD/APCs) before curing and decent EO coefficient when poled at 180 °C. However, after the films were poled at the crosslinking temperatures (200 °C or above), the transmissions of the waveguides and EO activity became very poor due to poling-induced chromophore degradation. By judicial molecular design of both chromophore and monomer structures to suppress thermal motion of polymer segments, we were able to realize the same or even better thermal stability in side-chain polymers CX2 and CX3. Since no curing is needed, devices can be poled at their optimal poling temperatures, and all good properties can be obtained simultaneously. Despite the excellent solubility in chlorinated solvents, these side-chain polymers are resistant to some other organic solvents or solutions such as acetone, photoresist and various UV-curable liquids.

A Bayesian Approach for Determining Protein Side-Chain Rotamer Conformations Using Unassigned NOE Data

PubMed Central

Zeng, Jianyang; Roberts, Kyle E.; Zhou, Pei

2011-01-01

Abstract A major bottleneck in protein structure determination via nuclear magnetic resonance (NMR) is the lengthy and laborious process of assigning resonances and nuclear Overhauser effect (NOE) cross peaks. Recent studies have shown that accurate backbone folds can be determined using sparse NMR data, such as residual dipolar couplings (RDCs) or backbone chemical shifts. This opens a question of whether we can also determine the accurate protein side-chain conformations using sparse or unassigned NMR data. We attack this question by using unassigned nuclear Overhauser effect spectroscopy (NOESY) data, which records the through-space dipolar interactions between protons nearby in three-dimensional (3D) space. We propose a Bayesian approach with a Markov random field (MRF) model to integrate the likelihood function derived from observed experimental data, with prior information (i.e., empirical molecular mechanics energies) about the protein structures. We unify the side-chain structure prediction problem with the side-chain structure determination problem using unassigned NMR data, and apply the deterministic dead-end elimination (DEE) and A* search algorithms to provably find the global optimum solution that maximizes the posterior probability. We employ a Hausdorff-based measure to derive the likelihood of a rotamer or a pairwise rotamer interaction from unassigned NOESY data. In addition, we apply a systematic and rigorous approach to estimate the experimental noise in NMR data, which also determines the weighting factor of the data term in the scoring function derived from the Bayesian framework. We tested our approach on real NMR data of three proteins: the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), and human ubiquitin. The promising results indicate that our algorithm can be applied in high-resolution protein structure determination. Since our approach does not require any NOE assignment, it can

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.

Arginine side chain stacking with peptide plane stabilizes the protein helix conformation in a cooperative way.

PubMed

Wang, Jia; Chen, Jingfei; Li, Jingwen; An, Liaoyuan; Wang, Yefei; Huang, Qingshan; Yao, Lishan

2018-06-01

A combined experimental and computational study is performed for arginine side chain stacking with the protein α-helix. Theremostability measurements of Aristaless homeodomain, a helical protein, suggest that mutating the arginine residue R106, R137 or R141, which has the guanidino side chain stacking with the peptide plane, to alanine, destabilizes the protein. The R-PP stacking has an energy of ∼0.2-0.4 kcal/mol. This stacking interaction mainly comes from dispersion and electrostatics, based on MP2 calculations with the energy decomposition analysis. The calculations also suggest that the stacking stabilizes 2 backbone-backbone h-bonds (i→i-4 and i-3→i-7) in a cooperative way. Desolvation and electrostatic polarization are responsible for cooperativity with the i→i-4 and i-3→i-7 h-bonds, respectively. This cooperativity is supported by a protein α-helices h-bond survey in the pdb databank where stacking shortens the corresponding h-bond distances. © 2018 Wiley Periodicals, Inc.

Ring flips revisited: (13)C relaxation dispersion measurements of aromatic side chain dynamics and activation barriers in basic pancreatic trypsin inhibitor.

PubMed

Weininger, Ulrich; Modig, Kristofer; Akke, Mikael

2014-07-22

Intramolecular motions of proteins are critical for biological function. Transient structural fluctuations underlie a wide range of processes, including enzyme catalysis, ligand binding to buried sites, and generic protein motions, such as 180° rotation of aromatic side chains in the protein interior, but remain poorly understood. Understanding the dynamics and molecular nature of concerted motions requires characterization of their rates and energy barriers. Here we use recently developed (13)C transverse relaxation dispersion methods to improve our current understanding of aromatic ring flips in basic pancreatic trypsin inhibitor (BPTI). We validate these methods by benchmarking ring-flip rates against the three previously characterized cases in BPTI, namely, Y23, Y35, and F45. Further, we measure conformational exchange for one additional aromatic ring, F22, which can be interpreted in terms of a flip rate of 666 s(-1) at 5 °C. Upon inclusion of our previously reported result that Y21 also flips slowly [Weininger, U., et al. (2013) J. Phys. Chem. B 117, 9241-9247], the (13)C relaxation dispersion experiments thus reveal relatively slow ring-flip rates for five of eight aromatic residues in BPTI. These results are in contrast with previous reports, which have estimated that all rings, except Y23, Y35, and F45, flip with a high rate at ambient temperature. The (13)C relaxation dispersion data result in an updated rank order of ring-flip rates in BPTI, which agrees considerably better with that estimated from a recent 1 ms molecular dynamics trajectory than do previously published NMR data. However, significant quantitative differences remain between experiment and simulation, in that the latter yields flip rates that are in many cases too fast by 1-2 orders of magnitude. By measuring flip rates across a temperature range of 5-65 °C, we determined the activation barriers of ring flips for Y23, Y35, and F45. Y23 and F45 have identical activation parameters

Cycloate, an inhibitor of fatty acid elongase, modulates the metabolism of very-long-side-chain alkylresorcinols in rye seedlings.

PubMed

Magnucka, Elzbieta G; Suzuki, Yoshikatsu; Pietr, Stanislaw J; Kozubek, Arkadiusz; Zarnowski, Robert

2009-10-01

Cycloate inhibits the biosynthesis of very-long-chain fatty acids, the essential constituents of plant waxes and suberin. Fatty acids also serve as precursors of aliphatic carbon chains in resorcinolic lipids, which play a fundamental role in the plant defence system against fungal pathogens. In this study, the effect of cycloate on the biosynthesis of 5-n-alkylresorcinols in rye seedlings (Secale cereale L.) grown under various light and thermal conditions was examined. The content of alkylresorcinols biosynthesised in rye was generally increased by the herbicide in both green and etiolated plants. The presence of cycloate also affected patterns of alkylresorcinol homologues in plants grown at 15 and 22 degrees C; very-long-side-chain compounds were less abundant, whereas both short-chain saturated and unsaturated homologues were generally accumulated. No cycloate-related effects caused by homologue pattern modifications were observed at elevated temperature. This study extends present understanding of the mode of action of thiocarbamate herbicides. Cycloate markedly affected the biosynthesis of very-long-side-chain resorcinolic lipids in rye seedlings, confirming the existence of parallels in both fatty acid and alkylresorcinol biosynthetic pathways. The observed cycloate-driven accumulation of 5-n-alkylresorcinols may improve the resistance of cereals to infections caused by microbial pathogens. Copyright 2009 Society of Chemical Industry.

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...

Synthesis of 2-Deoxybrassinosteroids Analogs with 24-nor, 22(S)-23-Dihydroxy-Type Side Chains from Hyodeoxycholic Acid.

PubMed

Carvajal, Rodrigo; González, Cesar; Olea, Andrés F; Fuentealba, Mauricio; Espinoza, Luis

2018-05-29

Natural brassinosteroids are widespread in the plant kingdom and it is known that they play an important role in regulating plant growth. In this study, two new brassinosteroid analogs with shorter side chains but keeping the diol function were synthesized. Thus, the synthesis of 2-deoxybrassinosteroids analogs of the 3α-hydroxy-24-nor, 22,23-dihydroxy-5α-cholestane side chain type is described. The starting material is a derivative from hyodeoxycholic acid ( 4 ), which was obtained with an overall yield of 59% following a previously reported five step route. The side chain of this intermediate was modified by oxidative decarboxylation to get a terminal olefin at the C22-C23 position (compound 20 ) and subsequent dihydroxylation of the olefin. The resulting epimeric mixture of 21a , 21b was separated and the absolute configuration at the C22 carbon for the main product 21a was elucidated by single crystal X-ray diffraction analysis of the benzoylated derivative 22 . Finally, lactonization of 21a through a Baeyer-Villiger oxidation of triacetylated derivative 23 , using CF₃CO₃H/CHCl₃ as oxidant system, leads to lactones 24 and 25 in 35% and 14% yields, respectively. Deacetylation of these compounds leads to 2-deoxybrassinosteroids 18 and 19 in 86% and 81% yields. Full structural characterization of all synthesized compounds was achieved using their 1D, 2D NMR, and HRMS data.

Can the Dielectric Constant of Fullerene Derivatives Be Enhanced by Side-Chain Manipulation? A Predictive First-Principles Computational Study.

PubMed

Sami, Selim; Haase, Pi A B; Alessandri, Riccardo; Broer, Ria; Havenith, Remco W A

2018-04-19

The low efficiency of organic photovoltaic (OPV) devices has often been attributed to the strong Coulombic interactions between the electron and hole, impeding the charge separation process. Recently, it has been argued that by increasing the dielectric constant of materials used in OPVs, this strong interaction could be screened. In this work, we report the application of periodic density functional theory together with the coupled perturbed Kohn-Sham method to calculate the electronic contribution to the dielectric constant for fullerene C 60 derivatives, a ubiquitous class of molecules in the field of OPVs. The results show good agreement with experimental data when available and also reveal an important undesirable outcome when manipulating the side chain to maximize the static dielectric constant: in all cases, the electronic contribution to the dielectric constant decreases as the side chain increases in size. This information should encourage both theoreticians and experimentalists to further investigate the relevance of contributions to the dielectric constant from slower processes like vibrations and dipolar reorientations for facilitating the charge separation, because electronically, enlarging the side chain of conventional fullerene derivatives only lowers the dielectric constant, and consequently, their electronic dielectric constant is upper bound by the one of C 60 .

Can the Dielectric Constant of Fullerene Derivatives Be Enhanced by Side-Chain Manipulation? A Predictive First-Principles Computational Study

PubMed Central

2018-01-01

The low efficiency of organic photovoltaic (OPV) devices has often been attributed to the strong Coulombic interactions between the electron and hole, impeding the charge separation process. Recently, it has been argued that by increasing the dielectric constant of materials used in OPVs, this strong interaction could be screened. In this work, we report the application of periodic density functional theory together with the coupled perturbed Kohn–Sham method to calculate the electronic contribution to the dielectric constant for fullerene C60 derivatives, a ubiquitous class of molecules in the field of OPVs. The results show good agreement with experimental data when available and also reveal an important undesirable outcome when manipulating the side chain to maximize the static dielectric constant: in all cases, the electronic contribution to the dielectric constant decreases as the side chain increases in size. This information should encourage both theoreticians and experimentalists to further investigate the relevance of contributions to the dielectric constant from slower processes like vibrations and dipolar reorientations for facilitating the charge separation, because electronically, enlarging the side chain of conventional fullerene derivatives only lowers the dielectric constant, and consequently, their electronic dielectric constant is upper bound by the one of C60. PMID:29561616

Predictions of the physicochemical properties of amino acid side chain analogs using molecular simulation.

PubMed

Ahmed, Alauddin; Sandler, Stanley I

2016-03-07

A candidate drug compound is released for clinical trails (in vivo activity) only if its physicochemical properties meet desirable bioavailability and partitioning criteria. Amino acid side chain analogs play vital role in the functionalities of protein and peptides and as such are important in drug discovery. We demonstrate here that the predictions of solvation free energies in water, in 1-octanol, and self-solvation free energies computed using force field-based expanded ensemble molecular dynamics simulation provide good accuracy compared to existing empirical and semi-empirical methods. These solvation free energies are then, as shown here, used for the prediction of a wide range of physicochemical properties important in the assessment of bioavailability and partitioning of compounds. In particular, we consider here the vapor pressure, the solubility in both water and 1-octanol, and the air-water, air-octanol, and octanol-water partition coefficients of amino acid side chain analogs computed from the solvation free energies. The calculated solvation free energies using different force fields are compared against each other and with available experimental data. The protocol here can also be used for a newly designed drug and other molecules where force field parameters and charges are obtained from density functional theory.

Side-chain conformational space analysis (SCSA): A multi conformation-based QSAR approach for modeling and prediction of protein-peptide binding affinities

NASA Astrophysics Data System (ADS)

Zhou, Peng; Chen, Xiang; Shang, Zhicai

2009-03-01

In this article, the concept of multi conformation-based quantitative structure-activity relationship (MCB-QSAR) is proposed, and based upon that, we describe a new approach called the side-chain conformational space analysis (SCSA) to model and predict protein-peptide binding affinities. In SCSA, multi-conformations (rather than traditional single-conformation) have received much attention, and the statistical average information on multi-conformations of side chains is determined using self-consistent mean field theory based upon side chain rotamer library. Thereby, enthalpy contributions (including electrostatic, steric, hydrophobic interaction and hydrogen bond) and conformational entropy effects to the binding are investigated in terms of occurrence probability of residue rotamers. Then, SCSA was applied into the dataset of 419 HLA-A*0201 binding peptides, and nonbonding contributions of each position in peptide ligands are well determined. For the peptides, the hydrogen bond and electrostatic interactions of the two ends are essential to the binding specificity, van der Waals and hydrophobic interactions of all the positions ensure strong binding affinity, and the loss of conformational entropy at anchor positions partially counteracts other favorable nonbonding effects.

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.

Exploiting the CNC side chain in heterocyclic rearrangements: synthesis of 4(5)-acylamino-imidazoles.

PubMed

Piccionello, Antonio Palumbo; Buscemi, Silvestre; Vivona, Nicolò; Pace, Andrea

2010-08-06

A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

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.

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.

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

Can 5-methylcytosine analogues with extended alkyl side chains guide DNA methylation?

PubMed

Kotandeniya, D; Seiler, C L; Fernandez, J; Pujari, S S; Curwick, L; Murphy, K; Wickramaratne, S; Yan, S; Murphy, D; Sham, Yuk Y; Tretyakova, N Y

2018-01-25

5-Methylcytosine ( Me C) is an endogenous modification of DNA that plays a crucial role in DNA-protein interactions, chromatin structure, epigenetic regulation, and DNA repair. Me C is produced via enzymatic methylation of the C-5 position of cytosine by DNA-methyltransferases (DNMT) which use S-adenosylmethionine (SAM) as a cofactor. Hemimethylated CG dinucleotides generated as a result of DNA replication are specifically recognized and methylated by maintenance DNA methyltransferase 1 (DNMT1). The accuracy of DNMT1-mediated methylation is essential for preserving tissue-specific DNA methylation and thus gene expression patterns. In the present study, we synthesized DNA duplexes containing MeC analogues with modified C-5 side chains and examined their ability to guide cytosine methylation by the human DNMT1 protein. We found that the ability of 5-alkylcytosines to direct cytosine methylation decreased with increased alkyl chain length and rigidity (methyl > ethyl > propyl ∼ vinyl). Molecular modeling studies indicated that this loss of activity may be caused by the distorted geometry of the DNA-protein complex in the presence of unnatural alkylcytosines.

Absolute Side-chain Structure at Position 13 Is Required for the Inhibitory Activity of Bromein*

PubMed Central

Sawano, Yoriko; Hatano, Ken-ichi; Miyakawa, Takuya; Tanokura, Masaru

2008-01-01

Bromelain isoinhibitor (bromein), a cysteine proteinase inhibitor from pineapple stem, has a unique double-chain structure. The bromein precursor protein includes three homologous inhibitor domains, each containing an interchain peptide between the light and heavy chains. The interchain peptide in the single-chain precursor is immediately processed by bromelain, a target proteinase. In the present study, to clarify the essential inhibitory site of bromein, we constructed 44 kinds of site-directed and deletion mutants and investigated the inhibitory activity of each toward bromelain. As a result, the complete chemical structure of Leu13 in the light chain was revealed to be essential for inhibition. Pro12 prior to the leucine residue was also involved in the inhibitory activity and would control the location of the leucine side chain by the fixed φ dihedral angle of proline. Furthermore, the five-residue length of the interchain peptide was strictly required for the inhibitory activity. On the other hand, no inhibitory activity against bromelain was observed by the substitution of proline for the N terminus residue Thr15 of the interchain peptide. In summary, these mutational analyses of bromein demonstrated that the appropriate position and conformation of Leu13 are absolutely crucial for bromelain inhibition. PMID:18948264

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

PubMed Central

Daigle, Maxime; Cantin, Katy

2014-01-01

Summary The synthesis and self-assembly of two new phenylacetylene macrocycle (PAM) organogelators were performed. Polar 2-hydroxyethoxy side chains were incorporated in the inner part of the macrocycles to modify the assembly mode in the gel state. With this modification, it was possible to increase the reactivity of the macrocycles in the xerogel state to form polydiacetylenes (PDAs), leading to a significant enhancement of the polymerization yields. The organogels and the PDAs were characterized using Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). PMID:25161718

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.

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.

Side-chain conformation of the M2 transmembrane peptide proton channel of influenza a virus from 19F solid-state NMR.

PubMed

Luo, Wenbin; Mani, Rajeswari; Hong, Mei

2007-09-13

The M2 transmembrane peptide (M2TMP) of the influenza A virus forms a tetrameric helical bundle that acts as a proton-selective channel important in the viral life cycle. The side-chain conformation of the peptide is largely unknown and is important for elucidating the proton-conducting mechanism and the channel stability. Using a 19F spin diffusion NMR technique called CODEX, we have measured the oligomeric states and interhelical side chain-side chain 19F-19F distances at several residues using singly fluorinated M2TMP bound to DMPC bilayers. 19F CODEX data at a key residue of the proton channel, Trp41, confirm the tetrameric state of the peptide and yield a nearest-neighbor interhelical distance of approximately 11 A under both neutral and acidic pH. Since the helix orientation is precisely known from previous 15N NMR experiments and the backbone channel diameter has a narrow allowed range, this 19F distance constrains the Trp41 side-chain conformation to t90 (chi1 approximately 180 degrees , chi2 approximately 90 degrees ). This Trp41 rotamer, combined with a previously measured 15N-13C distance between His37 and Trp411, suggests that the His37 rotamer is t-160. The implication of the proposed (His37, Trp41) rotamers to the gating mechanism of the M2 proton channel is discussed. Binding of the antiviral drug amantadine to the peptide does not affect the F-F distance at Trp41. Interhelical 19F-19F distances are also measured at residues 27 and 38, each mutated to 4-19F-Phe. For V27F-M2TMP, the 19F-19F distances suggest a mixture of dimers and tetramers, whereas the L38F-M2TMP data indicate two tetramers of different sizes, suggesting side chain conformational heterogeneity at this lipid-facing residue. This work shows that 19F spin diffusion NMR is a valuable tool for determining long-range intermolecular distances that shed light on the mechanism of action and conformational heterogeneity of membrane protein oligomers.

A fuzzy MICMAC analysis for improving supply chain performance of basic vaccines in developing countries.

PubMed

Chandra, Dheeraj; Kumar, Dinesh

2018-03-01

In recent years, demand to improve child immunization coverage globally, and the development of the latest vaccines and technology has made the vaccine market very complex. The rise in such complexities often gives birth to numerous issues in the vaccine supply chain, which are the primary cause of its poor performance. Figuring out the cause of the performance problem can help you decide how to address it. The goal of the present study is to identify and analyze important issues in the supply chain of basic vaccines required for child immunization in the developing countries. Twenty-five key issues as various factors of the vaccine supply chain have been presented in this paper. Fuzzy MICMAC analysis has been carried out to classify the factors based on their driving and dependence power and to develop a hierarchy based model. Further, the findings have been discussed with the field experts to identify the critical factors. Three factors: better demand forecast, communication between the supply chain members, and proper planning and scheduling have been identified as the critical factors of vaccine supply chain. These factors should be given special care to improve vaccine supply chain performance.

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

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.

Solid-state NMR Study Reveals Collagen I Structural Modifications of Amino Acid Side Chains upon Fibrillogenesis*

PubMed Central

De Sa Peixoto, Paulo; Laurent, Guillaume; Azaïs, Thierry; Mosser, Gervaise

2013-01-01

In vivo, collagen I, the major structural protein in human body, is found assembled into fibrils. In the present work, we study a high concentrated collagen sample in its soluble, fibrillar, and denatured states using one and two dimensional {1H}-13C solid-state NMR spectroscopy. We interpret 13C chemical shift variations in terms of dihedral angle conformation changes. Our data show that fibrillogenesis increases the side chain and backbone structural complexity. Nevertheless, only three to five rotameric equilibria are found for each amino acid residue, indicating a relatively low structural heterogeneity of collagen upon fibrillogenesis. Using side chain statistical data, we calculate equilibrium constants for a great number of amino acid residues. Moreover, based on a 13C quantitative spectrum, we estimate the percentage of residues implicated in each equilibrium. Our data indicate that fibril formation greatly affects hydroxyproline and proline prolyl pucker ring conformation. Finally, we discuss the implication of these structural data and propose a model in which the attractive force of fibrillogenesis comes from a structural reorganization of 10 to 15% of the amino acids. These results allow us to further understand the self-assembling process and fibrillar structure of collagen. PMID:23341452

Mechanical Behavior of Side-Chain Liquid Crystalline Networks

NASA Astrophysics Data System (ADS)

Gallani, J. L.; Hilliou, L.; Martinoty, P.; Doublet, F.; Mauzac, M.

1996-03-01

The mechanical properties of a homologue series of side-chain mesomorphic networks were studied with a piezo-rheometer over frequencies ranging from 10^{-2} Hz to 10^4 Hz. The results show that the compound's response is governed essentially by the dynamic glass transition. It is sensitive to the N-SmA transition, but insensitive to the N-I transition, with the result that the empirical principle of time-temperature superposition can be applied throughout the N-I transition. The influence of the crosslinking density and the amount of mesogenic side groups was also studied. For each of the samples, the static rigidity modulus G_0, the infinite-frequency dynamic rigidity modulus G_infty, and the characteristic frequencies respectively associated with the longest visco-elastic mode and the glass transition, were determined. Les propriétés mécaniques d'une série homologue de réseaux mésomorphes à chaînes latérales ont été étudiées avec un piézo-rhéomètre entre 10^{-2} Hz et 10^4 Hz. Les résultas obtenus montrent que la réponse du matériau est essentiellement gouvernée par la transition vitreuse dynamique; elle est sensible à la transition N-SmA mais insensible à la transition N-I de sorte qu'il est possible d'appliquer le principe empirique de superposition temps-température au travers de la transition N-I. L'influence du taux de réticulation et du taux de mésogènes a également été étudiée. Le module de rigidité statique G_0, le module de rigidité dynamique à fréquence infinie G_infty et les fréquences caractéristiques associées respectivement au mode viscoélastique le plus long et à la transition vitreuse, ont été déterminées pour chaque échantillon.

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.

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

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.

Effect of side-chain structure of rigid polyimide dispersant on mechanical properties of single-walled carbon nanotube/cyanate ester composite.

PubMed

Yuan, Wei; Li, Weifeng; Mu, Yuguang; Chan-Park, Mary B

2011-05-01

Three kinds of polymer, polyimide without side-chain (PI), polyimide-graft-glyceryl 4-nonylphenyl ether (PI-GNE), and polyimide-graft-bisphenol A diglyceryl acrylate (PI-BDA), have been synthesized and used to disperse single-walled carbon nanotubes (SWNTs) and to improve the interfacial bonding between SWNTs and cyanate ester (CE) matrix. Visual observation, UV-vis-near-IR (UV-vis-NIR) spectra, and atomic force microscopy (AFM) images show that both PI-GNE and PI-BDA are highly effective at dispersing and debundling SWNTs in DMF, whereas PI is less effective. Interaction between SWNTs and PI, PI-GNE or PI-BDA was confirmed by computer simulation and Raman spectra. A series of CE-based composite films reinforced with different loadings of SWNTs, SWNTs/PI, SWNTs/PI-GNE and SWNTs/PI-BDA were prepared by solution casting. It was found that, because of the unique side-chain structure of PI-BDA, SWNTs/PI-BDA disperse better in CE matrix than do SWNTs/PI-GNE, SWNTs/PI, and SWNTs. As a result, SWNTs/PI-BDA/CE composites have the greatest improvement in mechanical properties of the materials tested. These results imply that the choice of side-chain on a dispersant is very important to the dispersion of SWNTs in matrix and the filler/matrix interfacial adhesion, which are two key requirements for achieving effective reinforcement.

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

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.

Prediction of the interaction site on the surface of an isolated protein structure by analysis of side chain energy scores.

PubMed

Liang, Shide; Zhang, Jian; Zhang, Shicui; Guo, Huarong

2004-11-15

We show that residues at the interfaces of protein-protein complexes have higher side-chain energy than other surface residues. Eight different sets of protein complexes were analyzed. For each protein pair, the complex structure was used to identify the interface residues in the unbound monomer structures. Side-chain energy was calculated for each surface residue in the unbound monomer using our previously developed scoring function.1 The mean energy was calculated for the interface residues and the other surface residues. In 15 of the 16 monomers, the mean energy of the interface residues was higher than that of other surface residues. By decomposing the scoring function, we found that the energy term of the buried surface area of non-hydrogen-bonded hydrophilic atoms is the most important factor contributing to the high energy of the interface regions. In spite of lacking hydrophilic residues, the interface regions were found to be rich in buried non-hydrogen-bonded hydrophilic atoms. Although the calculation results could be affected by the inaccuracy of the scoring function, patch analysis of side-chain energy on the surface of an isolated protein may be helpful in identifying the possible protein-protein interface. A patch was defined as 20 residues surrounding the central residue on the protein surface, and patch energy was calculated as the mean value of the side-chain energy of all residues in the patch. In 12 of the studied monomers, the patch with the highest energy overlaps with the observed interface. The results are more remarkable when only three residues with the highest energy in a patch are averaged to derive the patch energy. All three highest-energy residues of the top energy patch belong to interfacial residues in four of the eight small protomers. We also found that the residue with the highest energy score on the surface of a small protomer is very possibly the key interaction residue. (c) 2004 Wiley-Liss, Inc.

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).

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.

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.

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.

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.

Molecular dynamics simulation of amino acid ionic liquids near a graphene electrode: effects of alkyl side-chain length.

PubMed

Sadeghi Moghadam, Behnoosh; Razmkhah, Mohammad; Hamed Mosavian, Mohammad Taghi; Moosavi, Fatemeh

2016-12-07

Electric double layer (EDL) supercapacitors, using ionic liquid electrolytes, have been receiving a great deal of attention in response to the growing demand for energy storage systems. In the present study, the nanoscopic structure of amino acid ionic liquids (AAILs) as biodegradable electrolytes near a neutral graphene surface was studied by molecular dynamics (MD) simulation. In order to explore the influence of the anion type and structure, the effect of the alkyl side-chain length of amino acids on the EDL was investigated. The results for the AAILs, composed of 1-ethyl-3-methylimidazolium ([EMIM]) cations near alanine ([ALA]) and isoleucine ([ILE]) anions, were compared to a conventional electrolyte, [EMIM][PF 6 ]. A lower mobility of AAIL compared to [EMIM][PF 6 ], with diffusions as low as 10 -11 m 2 s -1 , was observed. The structural results demonstrated a layered structure near the surface and most of the adsorbed imidazolium cation rings lay flat on the graphene surface. Both MD and quantum computations were performed to shed light on the charge behavior of AAIL electrolytes. As the current results demonstrate, an increase in the anion side-chain length leads to a decrease in both the number of adsorbed ions on the surface and the thickness of the first adsorbed layer. More impressively, it was observed that a low charge concentration in the EDL of AAILs is due to more side-side interactions. This remarkable feature could introduce AAILs as more efficient electrolyte materials than conventional [EMIM][PF 6 ].

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.

Diketopyrrolopyrrole-Based Conjugated Polymer Entailing Triethylene Glycols as Side Chains with High Thin-Film Charge Mobility without Post-Treatments

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

Yang, Si-Fen; Liu, Zi-Tong; Cai, Zheng-Xu

Side chain engineering of conjugated donor-acceptor polymers is a new way to manipulate their optoelectronic properties. Two new diketopyrrolopyrrole (DPP)-terthiophene-based conjugated polymers PDPP3T-1 and PDPP3T-2, with both hydrophilic triethylene glycol (TEG) and hydrophobic alkyl chains, are reported. It is demonstrated that the incorporation of TEG chains has a significant effect on the interchain packing and thin-film morphology with noticeable effect on charge transport. Polymer chains of PDPP3T-1 in which TEG chains are uniformly distributed can self-assemble spontaneously into a more ordered thin film. As a result, the thin film of PDPP3T-1 exhibits high saturated hole mobility up to 2.6 cm(2)more » V-1 s(-1) without any post-treatment. This is superior to those of PDPP3T with just alkyl chains and PDPP3T-2. Moreover, the respective field effect transistors made of PDPP3T-1 can be utilized for sensing ethanol vapor with high sensitivity (down to 100 ppb) and good selectivity.« less

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

Evidence of a reverse side-chain effect of tris(pentafluoroethyl)trifluorophosphate [FAP]-based ionic liquids against pathogenic bacteria.

PubMed

Weyhing-Zerrer, Nadine; Kalb, Roland; Oßmer, Rolf; Rossmanith, Peter; Mester, Patrick

2018-02-01

Increased interest in ionic liquids (ILs) is due to their designable and tunable unique physicochemical properties, which are utilized for a wide variety of chemical and biotechnological applications. ILs containing the tris(pentafluoroethyl)trifluorophosphate ([FAP]) anion have been shown to have excellent hydrolytic, electrochemical and thermal stability and have been successfully used in various applications. In the present study the influence of the cation on the toxicity of the [FAP] anion was investigated. Due to the properties of [FAP] ILs, the IL-toxicity of seven cations with [FAP] compared to [Cl] was examined by determination of minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) on six Gram-positive and six Gram-negative clinically-relevant bacteria. For the first time, to our knowledge, the results provide evidence for a decrease in toxicity with increasing alkyl side-chain length, indicating that the combination of both ions is responsible for this 'reverse side-chain effect'. These findings could portend development of new non-toxic ILs as green alternatives to conventional organic solvents. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

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.

Optocontrol of glutamate receptor activity by single side-chain photoisomerization

PubMed Central

Klippenstein, Viktoria; Hoppmann, Christian; Ye, Shixin; Wang, Lei; Paoletti, Pierre

2017-01-01

Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation. PSAA photoisomerization at the GluN1 clamshell hinge is sufficient to control glycine sensitivity and activation efficacy. Strikingly, in the pore domain, flipping of a M3 residue within a conserved transmembrane cavity impacts both gating and permeation properties. Our study demonstrates the first detection of molecular rearrangements in real-time due to the reversible light-switching of single amino acid side-chains, adding a dynamic dimension to protein site-directed mutagenesis. This novel approach to interrogate neuronal protein function has general applicability in the fast expanding field of optopharmacology. DOI: http://dx.doi.org/10.7554/eLife.25808.001 PMID:28534738

Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

PubMed

Ollikainen, Noah; de Jong, René M; Kortemme, Tanja

2015-01-01

Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

UV resonance Raman finds peptide bond-Arg side chain electronic interactions.

PubMed

Sharma, Bhavya; Asher, Sanford A

2011-05-12

We measured the UV resonance Raman excitation profiles and Raman depolarization ratios of the arginine (Arg) vibrations of the amino acid monomer as well as Arg in the 21-residue predominantly alanine peptide AAAAA(AAARA)(3)A (AP) between 194 and 218 nm. Excitation within the π → π* peptide bond electronic transitions result in UVRR spectra dominated by amide peptide bond vibrations. The Raman cross sections and excitation profiles indicate that the Arg side chain electronic transitions mix with the AP peptide bond electronic transitions. The Arg Raman bands in AP exhibit Raman excitation profiles similar to those of the amide bands in AP which are conformation specific. These Arg excitation profiles distinctly differ from the Arg monomer. The Raman depolarization ratios of Arg in monomeric solution are quite simple with ρ = 0.33 indicating enhancement by a single electronic transition. In contrast, we see very complex depolarization ratios of Arg in AP that indicate that the Arg residues are resonance enhanced by multiple electronic transitions.

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

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

Pursuing High-Mobility n-Type Organic Semiconductors by Combination of "Molecule-Framework" and "Side-Chain" Engineering.

PubMed

Zhang, Cheng; Zang, Yaping; Zhang, Fengjiao; Diao, Ying; McNeill, Christopher R; Di, Chong-An; Zhu, Xiaozhang; Zhu, Daoben

2016-10-01

"Molecule-framework" and "side-chain" engineering is powerful for the design of high-performance organic semiconductors. Based on 2DQTTs, the relationship between molecular structure, film microstructure, and charge-transport property in organic thin-film transistors (OTFTs) is studied. 2DQTT-o-B exhibits outstanding electron mobilities of 5.2 cm 2 V -1 s -1 , which is a record for air-stable solution-processable n-channel small-molecule OTFTs to date. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Controlling the Morphology of Side Chain Liquid Crystalline Block Copolymer Thin Films through Variations in Liquid Crystalline Content

PubMed Central

Verploegen, Eric; Zhang, Tejia; Jung, Yeon Sik; Ross, Caroline; Hammond, Paula T.

2009-01-01

In this paper we describe methods for manipulating the morphology of side-chain liquid crystalline block copolymers through variations in the liquid crystalline content. By systematically controlling the covalent attachment of side chain liquid crystals to a block copolymer (BCP) backbone, the morphology of both the liquid crystalline (LC) mesophase and the phase segregated BCP microstructures can be precisely manipulated. Increases in LC functionalization lead to stronger preferences for the anchoring of the LC mesophase relative to the substrate and the inter-material dividing surface (IMDS). By manipulating the strength of these interactions the arrangement and ordering of the ultrathin film block copolymer nanostructures can be controlled, yielding a range of morphologies that includes perpendicular and parallel cylinders, as well as both perpendicular and parallel lamellae. Additionally, we demonstrate the utilization of selective etching to create a nanoporous liquid crystalline polymer thin film. The unique control over the orientation and order of the self-assembled morphologies with respect to the substrate will allow for the custom design of thin films for specific nano-patterning applications without manipulation of the surface chemistry or the application of external fields. PMID:18763835

Controlling the morphology of side chain liquid crystalline block copolymer thin films through variations in liquid crystalline content.

PubMed

Verploegen, Eric; Zhang, Tejia; Jung, Yeon Sik; Ross, Caroline; Hammond, Paula T

2008-10-01

In this paper, we describe methods for manipulating the morphology of side-chain liquid crystalline block copolymers through variations in the liquid crystalline content. By systematically controlling the covalent attachment of side chain liquid crystals to a block copolymer (BCP) backbone, the morphology of both the liquid crystalline (LC) mesophase and the phase-segregated BCP microstructures can be precisely manipulated. Increases in LC functionalization lead to stronger preferences for the anchoring of the LC mesophase relative to the substrate and the intermaterial dividing surface. By manipulating the strength of these interactions, the arrangement and ordering of the ultrathin film block copolymer nanostructures can be controlled, yielding a range of morphologies that includes perpendicular and parallel cylinders, as well as both perpendicular and parallel lamellae. Additionally, we demonstrate the utilization of selective etching to create a nanoporous liquid crystalline polymer thin film. The unique control over the orientation and order of the self-assembled morphologies with respect to the substrate will allow for the custom design of thin films for specific nanopatterning applications without manipulation of the surface chemistry or the application of external fields.

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.

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.

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.

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.

Lattice model of linear telechelic polymer melts. II. Influence of chain stiffness on basic thermodynamic properties

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

Xu, Wen-Sheng, E-mail: wsxu@uchicago.edu; Freed, Karl F., E-mail: freed@uchicago.edu; Department of Chemistry, The University of Chicago, Chicago, Illinois 60637

2015-07-14

The lattice cluster theory (LCT) for semiflexible linear telechelic melts, developed in Paper I, is applied to examine the influence of chain stiffness on the average degree of self-assembly and the basic thermodynamic properties of linear telechelic polymer melts. Our calculations imply that chain stiffness promotes self-assembly of linear telechelic polymer melts that assemble on cooling when either polymer volume fraction ϕ or temperature T is high, but opposes self-assembly when both ϕ and T are sufficiently low. This allows us to identify a boundary line in the ϕ-T plane that separates two regions of qualitatively different influence of chainmore » stiffness on self-assembly. The enthalpy and entropy of self-assembly are usually treated as adjustable parameters in classical Flory-Huggins type theories for the equilibrium self-assembly of polymers, but they are demonstrated here to strongly depend on chain stiffness. Moreover, illustrative calculations for the dependence of the entropy density of linear telechelic polymer melts on chain stiffness demonstrate the importance of including semiflexibility within the LCT when exploring the nature of glass formation in models of linear telechelic polymer melts.« less

Chromatographic and mass spectral methods of identification for the side-chain and ring regioisomers of methylenedioxymethamphetamine.

PubMed

Aalberg, L; DeRuiter, J; Noggle, F T; Sippola, E; Clark, C R

2000-08-01

The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) is one of a total of 10 regioisomeric 2,3- and 3,4-methylenedioxyphenethylamines of MW 193 that yields regioisomeric fragment ions with equivalent mass (m/z 58 and 135/136) in the electron-impact (EI) mass spectrum. Thus, these 10 methylenedioxyphenethylamines are uniquely isomeric; they have the same molecular weight and equivalent major fragments in their mass spectra. The specific identification of one of these compounds (i.e., Ecstasy or 3,4-MDMA) in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This study reports the synthesis, chemical properties, spectral characterization, and chromatographic analysis of these 10 unique regioisomers. The ten 2,3- and 3,4-regioisomers of MDMA are synthesized from commercially available precursor chemicals. In the EI mass spectra, the side-chain regioisomers show some variation in the relative intensity of the major ions, with the exception of only one or two minor ions that might be considered side-chain specific fragments. The position of substitution for the methylenedioxy ring is not easily determined by mass spectral techniques, and the ultimate identification of any one of these amines with the elimination of the other nine must depend heavily upon chromatographic methods. The chromatographic separation of these 10 uniquely regioisomeric amines are studied using reversed-phase liquid chromatographic methods with gradient elution and gas chromatographic techniques with temperature program optimization.

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

Proton clouds to measure long-range contacts between nonexchangeable side chain protons in solid-state NMR.

PubMed

Sinnige, Tessa; Daniëls, Mark; Baldus, Marc; Weingarth, Markus

2014-03-26

We show that selective labeling of proteins with protonated amino acids embedded in a perdeuterated matrix, dubbed 'proton clouds', provides general access to long-range contacts between nonexchangeable side chain protons in proton-detected solid-state NMR, which is important to study protein tertiary structure. Proton-cloud labeling significantly improves spectral resolution by simultaneously reducing proton line width and spectral crowding despite a high local proton density in clouds. The approach is amenable to almost all canonical amino acids. Our method is demonstrated on ubiquitin and the β-barrel membrane protein BamA.

Identification of Oxygenated Fatty Acid as a Side Chain of Lipo-Alkaloids in Aconitum carmichaelii by UHPLC-Q-TOF-MS and a Database.

PubMed

Liang, Ying; Wu, Jian-Lin; Leung, Elaine Lai-Han; Zhou, Hua; Liu, Zhongqiu; Yan, Guanyu; Liu, Ying; Liu, Liang; Li, Na

2016-03-31

Lipo-alkaloid is a kind of C19-norditerpenoid alkaloid usually found in Aconitum species. Structurally, they contain an aconitane skeleton and one or two fatty acid moieties of 3-25 carbon chains with 1-6 unsaturated degrees. Analysis of the lipo-alkaloids in roots of Aconitum carmichaelii resulted in the isolation of six known pure lipo-alkaloids (A1-A6) and a lipo-alkaloid mixture (A7). The mixture shared the same aconitane skeleton of 14-benzoylmesaconine, but their side chains were determined to be 9-hydroxy-octadecadienoic acid, 13-hydroxy-octadecadienoic acid and 10-hydroxy-octadecadienoic acid, respectively, by MS/MS analysis after alkaline hydrolysis. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. In order to identify more lipo-alkaloids, a compound database was established based on various combinations between the aconitane skeleton and the fatty acid chain, and then, the identification of lipo-alkaloids was conducted using the database, UHPLC-Q-TOF-MS and MS/MS. Finally, 148 lipo-alkaloids were identified from A. carmichaelii after intensive MS/MS analysis, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties.

Effects of side chains in helix nucleation differ from helix propagation

PubMed Central

Miller, Stephen E.; Watkins, Andrew M.; Kallenbach, Neville R.; Arora, Paramjit S.

2014-01-01

Helix–coil transition theory connects observable properties of the α-helix to an ensemble of microstates and provides a foundation for analyzing secondary structure formation in proteins. Classical models account for cooperative helix formation in terms of an energetically demanding nucleation event (described by the σ constant) followed by a more facile propagation reaction, with corresponding s constants that are sequence dependent. Extensive studies of folding and unfolding in model peptides have led to the determination of the propagation constants for amino acids. However, the role of individual side chains in helix nucleation has not been separately accessible, so the σ constant is treated as independent of sequence. We describe here a synthetic model that allows the assessment of the role of individual amino acids in helix nucleation. Studies with this model lead to the surprising conclusion that widely accepted scales of helical propensity are not predictive of helix nucleation. Residues known to be helix stabilizers or breakers in propagation have only a tenuous relationship to residues that favor or disfavor helix nucleation. PMID:24753597

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

Computational mining for hypothetical patterns of amino acid side chains in protein data bank (PDB)

NASA Astrophysics Data System (ADS)

Ghani, Nur Syatila Ab; Firdaus-Raih, Mohd

2018-04-01

The three-dimensional structure of a protein can provide insights regarding its function. Functional relationship between proteins can be inferred from fold and sequence similarities. In certain cases, sequence or fold comparison fails to conclude homology between proteins with similar mechanism. Since the structure is more conserved than the sequence, a constellation of functional residues can be similarly arranged among proteins of similar mechanism. Local structural similarity searches are able to detect such constellation of amino acids among distinct proteins, which can be useful to annotate proteins of unknown function. Detection of such patterns of amino acids on a large scale can increase the repertoire of important 3D motifs since available known 3D motifs currently, could not compensate the ever-increasing numbers of uncharacterized proteins to be annotated. Here, a computational platform for an automated detection of 3D motifs is described. A fuzzy-pattern searching algorithm derived from IMagine an Amino Acid 3D Arrangement search EnGINE (IMAAAGINE) was implemented to develop an automated method for searching of hypothetical patterns of amino acid side chains in Protein Data Bank (PDB), without the need for prior knowledge on related sequence or structure of pattern of interest. We present an example of the searches, which is the detection of a hypothetical pattern derived from known structural motif of C2H2 structural pattern from zinc fingers. The conservation of particular patterns of amino acid side chains in unrelated proteins is highlighted. This approach can act as a complementary method for available structure- and sequence-based platforms and may contribute in improving functional association between proteins.

Quantitative expression of protein heterogeneity: Response of amino acid side chains to their local environment.

PubMed

Bandyopadhyay, Debashree; Mehler, Ernest L

2008-08-01

A general method has been developed to characterize the hydrophobicity or hydrophilicity of the microenvironment (MENV), in which a given amino acid side chain is immersed, by calculating a quantitative property descriptor (QPD) based on the relative (to water) hydrophobicity of the MENV. Values of the QPD were calculated for a test set of 733 proteins to analyze the modulating effects on amino acid residue properties by the MENV in which they are imbedded. The QPD values and solvent accessibility were used to derive a partitioning of residues based on the MENV hydrophobicities. From this partitioning, a new hydrophobicity scale was developed, entirely in the context of protein structure, where amino acid residues are immersed in one or more "MENVpockets." Thus, the partitioning is based on the residues "sampling" a large number of "solvents" (MENVs) that represent a very large range of hydrophobicity values. It was found that the hydrophobicity of around 80% of amino acid side chains and their MENV are complementary to each other, but for about 20%, the MENV and their imbedded residue can be considered as mismatched. Many of these mismatches could be rationalized in terms of the structural stability of the protein and/or the involvement of the imbedded residue in function. The analysis also indicated a remarkable conservation of local environments around highly conserved active site residues that have similar functions across protein families, but where members have relatively low sequence homology. Thus, quantitative evaluation of this QPD is suggested, here, as a tool for structure-function prediction, analysis, and parameter development for the calculation of properties in proteins. (c) 2008 Wiley-Liss, Inc.

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

Precise Side-Chain Engineering of Thienylenevinylene-Benzotriazole-Based Conjugated Polymers with Coplanar Backbone for Organic Field Effect Transistors and CMOS-like Inverters.

PubMed

Lee, Min-Hye; Kim, Juhwan; Kang, Minji; Kim, Jihong; Kang, Boseok; Hwang, Hansu; Cho, Kilwon; Kim, Dong-Yu

2017-01-25

Two donor-acceptor (D-A) alternating conjugated polymers based on thienylenevinylene-benzotriazole (TV-BTz), PTV6B with a linear side chain and PTVEhB with a branched side chain, were synthesized and characterized for organic field effect transistors (OFETs) and complementary metal-oxide-semiconductor (CMOS)-like inverters. According to density functional theory (DFT), polymers based on TV-BTz exhibit a coplanar and rigid structure with no significant twists, which could cause to an increase in charge-carrier mobility in OFETs. Alternating alkyl side chains of the polymers impacted neither the band gap nor the energy level. However, it significantly affected the morphology and crystallinity when the polymer films were thermally annealed. To investigate the effect of thermal annealing on the morphology and crystallinity, we characterized the polymer films using atomic force microscopy (AFM) and 2D-grazing incidence X-ray diffraction (2D-GIWAXD). Fibrillary morphologies with larger domains and increased crystallinity were observed in the polymer films after thermal annealing. These polymers exhibited improved charge-carrier mobilities in annealed films at 200 °C and demonstrated optimal OFET device performance with p-type transport characteristics with charge-carrier mobilities of 1.51 cm 2 /(V s) (PTV6B) and 2.58 cm 2 /(V s) (PTVEhB). Furthermore, CMOS-like inorganic (ZnO)-organic (PTVEhB) hybrid bilayer inverter showed that the inverting voltage (V inv ) was positioned near the ideal switching point at half (1/2) of supplied voltage (V DD ) due to fairly balanced p- and n-channels.

A Message Passing Approach to Side Chain Positioning with Applications in Protein Docking Refinement *

PubMed Central

Moghadasi, Mohammad; Kozakov, Dima; Mamonov, Artem B.; Vakili, Pirooz; Vajda, Sandor; Paschalidis, Ioannis Ch.

2013-01-01

We introduce a message-passing algorithm to solve the Side Chain Positioning (SCP) problem. SCP is a crucial component of protein docking refinement, which is a key step of an important class of problems in computational structural biology called protein docking. We model SCP as a combinatorial optimization problem and formulate it as a Maximum Weighted Independent Set (MWIS) problem. We then employ a modified and convergent belief-propagation algorithm to solve a relaxation of MWIS and develop randomized estimation heuristics that use the relaxed solution to obtain an effective MWIS feasible solution. Using a benchmark set of protein complexes we demonstrate that our approach leads to more accurate docking predictions compared to a baseline algorithm that does not solve the SCP. PMID:23515575

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.

Proteolytic processing of the pro beta chain of beta-hexosaminidase occurs at basic residues contained within an exposed disulfide loop structure.

PubMed

Sagherian, C; Poroszlay, S; Vavougios, G; Mahuran, D

1993-01-01

Lysosomal beta-hexosaminidase (EC 3.2.1.52) occurs as two major isozymes, Hex A (alpha beta) and Hex B (beta beta). The alpha and beta subunits are encoded by the HEXA and HEXB genes, respectively. Extensive homology in both the gene structures and deduced primary sequences demonstrate their common evolutionary origin. While undergoing similar proteolytic modifications in the lysosome, the pro beta polypeptide is additionally cleaved internally to produce the mature 24-30 kilodalton beta b and beta a chains. Previous data have suggested that this processing event occurs somewhere between residues Ser311 and Lys315. In this report we demonstrate that this area is located in a hydrophilic disulfide-loop structure (between Cys309 and Cys360). The cleavage event is prevented by the deletion through in vitro mutagenesis of the Arg312-Gln-Asn-Lys tetrapeptide or by its substitution with the aligned alpha residues (Gly-Ser-Glu-Pro). Reintroduction of either Arg312 or Lys315 reinstates the processing. Furthermore, we show that this area is not involved in lysosomal targeting of pro-Hex B, or in the increased stability or the variation in substrate specificity of the beta as compared with the alpha subunit. Our data suggest the presence of a novel lysosomal endoprotease. Like other endoproteases it is specific for basic amino acids; however, it cleaves on the amino-terminal side rather than the conventional carboxy-terminal side of such residues and then only if they are fully exposed to the lysosomal environment.(ABSTRACT TRUNCATED AT 250 WORDS)

The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors.

PubMed

Nielsen, Bjørn G; Jensen, Morten Ø; Bohr, Henrik G

2003-01-01

The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analysis in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity of [Leu]enkephalin and [Met]enkephalin to the known mu- and delta-type opiate receptors to which they bind as agonists. Other plausible consequences of these probability distributions are discussed in relation to the way in which they may influence the dynamics of the synapse. Copyright 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71: 577-592, 2003

Phenylpropanoid 2,3-dioxygenase involved in the cleavage of the ferulic acid side chain to form vanillin and glyoxylic acid in Vanilla planifolia.

PubMed

Negishi, Osamu; Negishi, Yukiko

2017-09-01

Enzyme catalyzing the cleavage of the phenylpropanoid side chain was partially purified by ion exchange and gel filtration column chromatography after (NH 4 ) 2 SO 4 precipitation. Enzyme activities were dependent on the concentration of dithiothreitol (DTT) or glutathione (GSH) and activated by addition of 0.5 mM Fe 2+ . Enzyme activity for ferulic acid was as high as for 4-coumaric acid in the presence of GSH, suggesting that GSH acts as an endogenous reductant in vanillin biosynthesis. Analyses of the enzymatic reaction products with quantitative NMR (qNMR) indicated that an amount of glyoxylic acid (GA) proportional to vanillin was released from ferulic acid by the enzymatic reaction. These results suggest that phenylpropanoid 2,3-dioxygenase is involved in the cleavage of the ferulic acid side chain to form vanillin and GA in Vanilla planifolia.

Design, synthesis and biological evaluation of paclitaxel-mimics possessing only the oxetane D-ring and side chain structures.

PubMed

Chen, Xing-Xiu; Gao, Feng; Wang, Qi; Huang, Xing; Wang, Dan

2014-01-01

Two spiro paclitaxel-mimics consisting only of an oxetane D-ring and a C-13 side chain were designed and synthesized on the basis of analysis of structure-activity relationships (SAR) of paclitaxel. In vitro microtubule-stabilizing and antiproliferative assays indicated a moderate weaker activity of the mimics than paclitaxel, but which still represented the first example of simplified paclitaxel analogues with significant anti-tumor biological activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Side chain requirements for affinity and specificity in D5, an HIV-1 antibody derived from the VH1-69 germline segment.

PubMed

Stewart, Alex; Harrison, Joseph S; Regula, Lauren K; Lai, Jonathan R

2013-04-08

Analysis of factors contributing to high affinity antibody-protein interactions provides insight into natural antibody evolution, and guides the design of antibodies with new or enhanced function. We previously studied the interaction between antibody D5 and its target, a designed protein based on HIV-1 gp41 known as 5-Helix, as a model system [Da Silva, G. F.; Harrison, J. S.; Lai, J. R., Biochemistry, 2010, 49, 5464-5472]. Antibody D5 represents an interesting case study because it is derived from the VH1-69 germline segment; this germline segment is characterized by a hydrophobic second heavy chain complementarity determining region (HCDR2) that constitutes the major functional paratope in D5 and several antibodies derived from the same progenitor. Here we explore side chain requirements for affinity and specificity in D5 using phage display. Two D5-based libraries were prepared that contained diversity in all three light chain complementarity determining regions (LCDRs 1-3), and in the third HCDR (HCDR3). The first library allowed residues to vary among a restricted set of six amino acids (Tyr/Ala/Asp/Ser/His/Pro; D5-Lib-I). The second library was designed based on a survey of existing VH1-69 antibody structures (D5-Lib-II). Both libraries were subjected to multiple rounds of selection against 5-Helix, and individual clones characterized. We found that selectants from D5-Lib-I generally had moderate affinity and specificity, while many clones from D5-Lib-II exhibited D5-like properties. Additional analysis of the D5-Lib-II functional population revealed position-specific biases for particular amino acids, many that differed from the identity of those side chains in D5. Together these results suggest that there is some permissiveness for alternative side chains in the LCDRs and HCDR3 of D5, but that replacement with a minimal set of residues is not tolerated in this scaffold for 5-Helix recognition. This work provides novel information about this high

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.

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.

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.

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

Nano-Mole Scale Side-Chain Signal Assignment by 1H-Detected Protein Solid-State NMR by Ultra-Fast Magic-Angle Spinning and Stereo-Array Isotope Labeling

PubMed Central

Nishiyama, Yusuke; Endo, Yuki; Nemoto, Takahiro; Yamauchi, Kazuo; Asakura, Tetsuo; Takeda, Mitsuhiro; Terauchi, Tsutomu; Kainosho, Masatsune; Ishii, Yoshitaka

2015-01-01

We present a general approach in 1H-detected 13C solid-state NMR (SSNMR) for side-chain signal assignments of 10-50 nmol quantities of proteins using a combination of a high magnetic field, ultra-fast magic-angle spinning (MAS) at ~80 kHz, and stereo-array-isotope-labeled (SAIL) proteins [Kainosho M. et al., Nature 440, 52–57, 2006]. First, we demonstrate that 1H indirect detection improves the sensitivity and resolution of 13C SSNMR of SAIL proteins for side-chain assignments in the ultra-fast MAS condition. 1H-detected SSNMR was performed for micro-crystalline ubiquitin (~55 nmol or ~0.5mg) that was SAIL-labeled at seven isoleucine (Ile) residues. Sensitivity was dramatically improved by 1H-detected 2D 1H/13C SSNMR by factors of 5.4-9.7 and 2.1-5.0, respectively, over 13C-detected 2D 1H/13C SSNMR and 1D 13C CPMAS, demonstrating that 2D 1H-detected SSNMR offers not only additional resolution but also sensitivity advantage over 1D 13C detection for the first time. High 1H resolution for the SAIL-labeled side-chain residues offered reasonable resolution even in the 2D data. A 1H-detected 3D 13C/13C/1H experiment on SAIL-ubiquitin provided nearly complete 1H and 13C assignments for seven Ile residues only within ~2.5 h. The results demonstrate the feasibility of side-chain signal assignment in this approach for as little as 10 nmol of a protein sample within ~3 days. The approach is likely applicable to a variety of proteins of biological interest without any requirements of highly efficient protein expression systems. PMID:25856081

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.

Long-range dynamic effects of point mutations propagate through side chains in the serine protease inhibitor eglin c.

PubMed

Clarkson, Michael W; Lee, Andrew L

2004-10-05

Long-range interactions are fundamental to protein behaviors such as cooperativity and allostery. In an attempt to understand the role protein flexibility plays in such interactions, the distribution of local fluctuations in a globular protein was monitored in response to localized, nonelectrostatic perturbations. Two valine-to-alanine mutations were introduced into the small serine protease inhibitor eglin c, and the (15)N and (2)H NMR spin relaxation properties of these variants were analyzed in terms of the Lipari-Szabo dynamics formalism and compared to those of the wild type. Significant changes in picosecond to nanosecond dynamics were observed in side chains located as much as 13 A from the point of mutation. Additionally, those residues experiencing altered dynamics appear to form contiguous surfaces within the protein. In the case of V54A, the large-to-small mutation results in a rigidification of connected residues, even though this mutation decreases the global stability. These findings suggest that dynamic perturbations arising from single mutations may propagate away from the perturbed site through networks of interacting side chains. That this is observed in eglin c, a classically nonallosteric protein, suggests that such behavior will be observed in many, if not all, globular proteins. Differences in behavior between the two mutants suggest that dynamic responses will be context-dependent.

Progress in protein-protein docking: atomic resolution predictions in the CAPRI experiment using RosettaDock with an improved treatment of side-chain flexibility.

PubMed

Schueler-Furman, Ora; Wang, Chu; Baker, David

2005-08-01

RosettaDock uses real-space Monte Carlo minimization (MCM) on both rigid-body and side-chain degrees of freedom to identify the lowest free energy docked arrangement of 2 protein structures. An improved version of the method that uses gradient-based minimization for off-rotamer side-chain optimization and includes information from unbound structures was used to create predictions for Rounds 4 and 5 of CAPRI. First, large numbers of independent MCM trajectories were carried out and the lowest free energy docked configurations identified. Second, new trajectories were started from these lowest energy structures to thoroughly sample the surrounding conformation space, and the lowest energy configurations were submitted as predictions. For all cases in which there were no significant backbone conformational changes, a small number of very low-energy configurations were identified in the first, global search and subsequently found to be close to the center of the basin of attraction in the free energy landscape in the second, local search. Following the release of the experimental coordinates, it was found that the centers of these free energy minima were remarkably close to the native structures in not only the rigid-body orientation but also the detailed conformations of the side-chains. Out of 8 targets, the lowest energy models had interface root-mean-square deviations (RMSDs) less than 1.1 A from the correct structures for 6 targets, and interface RMSDs less than 0.4 A for 3 targets. The predictions were top submissions to CAPRI for Targets 11, 12, 14, 15, and 19. The close correspondence of the lowest free energy structures found in our searches to the experimental structures suggests that our free energy function is a reasonable representation of the physical chemistry, and that the real space search with full side-chain flexibility to some extent solves the protein-protein docking problem in the absence of significant backbone conformational changes. On the

Variation of the net charge, lipophilicity, and side chain flexibility in Dmt(1)-DALDA: Effect on Opioid Activity and Biodistribution.

PubMed

Novoa, Alexandre; Van Dorpe, Sylvia; Wynendaele, Evelien; Spetea, Mariana; Bracke, Nathalie; Stalmans, Sofie; Betti, Cecilia; Chung, Nga N; Lemieux, Carole; Zuegg, Johannes; Cooper, Matthew A; Tourwé, Dirk; De Spiegeleer, Bart; Schiller, Peter W; Ballet, Steven

2012-11-26

The influence of the side chain charges of the second and fourth amino acid residues in the peptidic μ opioid lead agonist Dmt-d-Arg-Phe-Lys-NH(2) ([Dmt(1)]-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt(1)]-DALDA and to investigate the Phe(3) side chain flexibility, the final amide bond was N-methylated and Phe(3) was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (ip and sc) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity, and transport properties. Strikingly, while [Dmt(1)]-DALDA and its N-methyl analogue, Dmt-d-Arg-Phe-NMeLys-NH(2), showed a long-lasting antinociceptive effect (>7 h), the peptides with d-Cit(2) generate potent antinociception more rapidly (maximal effect at 1h postinjection) but also lose their analgesic activity faster when compared to [Dmt(1)]-DALDA and [Dmt(1),NMeLys(4)]-DALDA.

Variation of the net charge, lipophilicity and side chain flexibility in Dmt1-DALDA: effect on opioid activity and biodistribution

PubMed Central

Novoa, Alexandre; Van Dorpe, Sylvia; Wynendaele, Evelien; Spetea, Mariana; Bracke, Nathalie; Stalmans, Sofie; Betti, Cecilia; Chung, Nga N.; Lemieux, Carole; Zuegg, Johannes; Cooper, Matthew A.; Tourwé, Dirk; De Spiegeleer, Bart; Schiller, Peter W.; Ballet, Steven

2012-01-01

The influence of the side chain charges of the second and fourth amino acid residues in the peptidic μ opioid lead agonist Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt1]-DALDA and to investigate the Phe3 side chain flexibility, the final amide bond was N-methylated and Phe3 was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (i.p. and s.c.) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity and transport properties. Strikingly, while [Dmt1]-DALDA and its N-methyl analogue, Dmt-D-Arg-Phe-NMeLys-NH2, showed a long-lasting antinociceptive effect (>7h), the peptides with D-Cit2 generate potent antinociception more rapidly (maximal effect at 1h post-injection) but also lose their analgesic activity faster, when compared to [Dmt1]-DALDA and [Dmt1,NMeLys4]-DALDA. PMID:23102273

Developing Potential Energy Curves of Acidic and Basic Amino Acids Using Quantum Computational Techniques

NASA Astrophysics Data System (ADS)

de Guzman, C. P.; Andrianarijaona, M.; Yoshida, Y.; Kim, K.; Andrianarijaona, V. M.

2017-04-01

Proteins are made out of long chains of amino acids and are an integral part of many tasks of a cell. Because the function of a protein is caused by its structure, even minute changes in the molecular geometry of the protein can have large effects on how the protein can be used. This study investigated how manipulations in the structure of acidic and basic amino acids affected their potential energy. Acidic and basic amino acids were chosen because prior studies have suggested that the ionizable side chains of these amino acids can be very influential on a molecule's prefered conformation. Each atom in the molecule was pulled along x, y, and z axis to see how different types of changes affect the potential energy of the whole structure. The results of our calculations, which were done using ORCA, emphasize the vibronic couplings. The aggregated data was used to create a data set of potential energy curves to better understand the quantum dynamic properties of acidic and basic amino acids (preliminary data was presented in http://meetings.aps.org/Meeting/MAR16/Session/M1.273 andhttp://meetings.aps.org/Meeting/FWS16/Session/F2.6).

In vitro and In vivo Antimalarial Activity of Amphiphilic Naphthothiazolium Salts with Amine-Bearing Side Chains

PubMed Central

Ulrich, Peter; Gipson, Gregory R.; Clark, Martha A.; Tripathi, Abhai; Sullivan, David J.; Cerami, Carla

2014-01-01

Because of emerging resistance to existing drugs, new chemical classes of antimalarial drugs are urgently needed. We have rationally designed a library of compounds that were predicted to accumulate in the digestive vacuole and then decrystallize hemozoin by breaking the iron carboxylate bond in hemozoin. We report the synthesis of 16 naphthothiazolium salts with amine-bearing side chains and their activities against the erythrocytic stage of Plasmodium falciparum in vitro. KSWI-855, the compound with the highest efficacy against the asexual stages of P. falciparum in vitro, also had in vitro activity against P. falciparum gametocytes and in vivo activity against P. berghei in a murine malaria model. PMID:25184829

Enhanced Basicity of Push-Pull Nitrogen Bases in the Gas Phase.

PubMed

Raczyńska, Ewa D; Gal, Jean-François; Maria, Pierre-Charles

2016-11-23

Nitrogen bases containing one or more pushing amino-group(s) directly linked to a pulling cyano, imino, or phosphoimino group, as well as those in which the pushing and pulling moieties are separated by a conjugated spacer (C═X) n , where X is CH or N, display an exceptionally strong basicity. The n-π conjugation between the pushing and pulling groups in such systems lowers the basicity of the pushing amino-group(s) and increases the basicity of the pulling cyano, imino, or phosphoimino group. In the gas phase, most of the so-called push-pull nitrogen bases exhibit a very high basicity. This paper presents an analysis of the exceptional gas-phase basicity, mostly in terms of experimental data, in relation with structure and conjugation of various subfamilies of push-pull nitrogen bases: nitriles, azoles, azines, amidines, guanidines, vinamidines, biguanides, and phosphazenes. The strong basicity of biomolecules containing a push-pull nitrogen substructure, such as bioamines, amino acids, and peptides containing push-pull side chains, nucleobases, and their nucleosides and nucleotides, is also analyzed. Progress and perspectives of experimental determinations of GBs and PAs of highly basic compounds, termed as "superbases", are presented and benchmarked on the basis of theoretical calculations on existing or hypothetical molecules.

Block copolymer micelles with acid-labile ortho ester side-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells.

PubMed

Tang, Rupei; Ji, Weihang; Panus, David; Palumbo, R Noelle; Wang, Chun

2011-04-10

A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b-PEYM micelles assumed a stable core-shell structure in aqueous buffer at physiological pH with a low critical micelle concentration as determined by proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho ester side-chain at physiological pH was minimal yet much accelerated at mildly acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4 and was released at a much higher rate in response to slight acidification to pH 5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic profile, consisting of an initial fast phase of several hours followed by a sustained release period of several days. Dox loaded in the micelles was rapidly taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome and subsequently in the nucleus in a few hours, in contrast to the very low uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox-loaded micelles was determined by the MTT assay and compared with that of the free Dox. While the empty micelles themselves were not toxic, the IC(50) values of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times (by 48h) lower than the free drug. The much enhanced potency in killing the multi-drug-resistant human glioma cells by Dox loaded in the micelles could be attributed to high intracellular drug concentration and the subsequent pH-triggered drug release. These results

Removal of acidic or basic α-amino acids in water by poorly water soluble scandium complexes.

PubMed

Hayashi, Nobuyuki; Jin, Shigeki; Ujihara, Tomomi

2012-11-02

To recognize α-amino acids with highly polar side chains in water, poorly water soluble scandium complexes with both Lewis acidic and basic portions were synthesized as artificial receptors. A suspension of some of these receptor molecules in an α-amino acid solution could remove acidic and basic α-amino acids from the solution. The compound most efficient at preferentially removing basic α-amino acids (arginine, histidine, and lysine) was the receptor with 7,7'-[1,3-phenylenebis(carbonylimino)]bis(2-naphthalenesulfonate) as the ligand. The neutral α-amino acids were barely removed by these receptors. Removal experiments using a mixed amino acid solution generally gave results similar to those obtained using solutions containing a single amino acid. The results demonstrated that the scandium complex receptors were useful for binding acidic and basic α-amino acids.

Rotator side chains trigger cooperative transition for shape and function memory effect in organic semiconductors.

PubMed

Chung, Hyunjoong; Dudenko, Dmytro; Zhang, Fengjiao; D'Avino, Gabriele; Ruzié, Christian; Richard, Audrey; Schweicher, Guillaume; Cornil, Jérôme; Beljonne, David; Geerts, Yves; Diao, Ying

2018-01-18

Martensitic transition is a solid-state phase transition involving cooperative movement of atoms, mostly studied in metallurgy. The main characteristics are low transition barrier, ultrafast kinetics, and structural reversibility. They are rarely observed in molecular crystals, and hence the origin and mechanism are largely unexplored. Here we report the discovery of martensitic transition in single crystals of two different organic semiconductors. In situ microscopy, single-crystal X-ray diffraction, Raman and nuclear magnetic resonance spectroscopy, and molecular simulations combined indicate that the rotating bulky side chains trigger cooperative transition. Cooperativity enables shape memory effect in single crystals and function memory effect in thin film transistors. We establish a molecular design rule to trigger martensitic transition in organic semiconductors, showing promise for designing next-generation smart multifunctional materials.

Asymmetric synthesis of the HMG-CoA reductase inhibitor atorvastatin calcium: an organocatalytic anhydride desymmetrization and cyanide-free side chain elongation approach.

PubMed

Chen, Xiaofei; Xiong, Fangjun; Chen, Wenxue; He, Qiuqin; Chen, Fener

2014-03-21

An efficient asymmetric synthesis of atorvastatin calcium has been achieved from commercially available diethyl 3-hydroxyglutarate through a novel approach that involves an organocatalytic enantioselective cyclic anhydride desymmetrization to establish C(3) stereogenicity and cyanide-free assembly of C7 amino type side chain via C5+C2 strategy as the key transformations.

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.

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.

Digestion by fungal glycanases of arabinoxylans with different feruloylated side-chains.

PubMed

Wende, G; Fry, S C

1997-07-01

Alcohol-insoluble residues (AIRs) from Festuca and Zea cell cultures contained 7.4 and 35 nmol esterified ferulate mg-1, respectively. Driselase solubilised 79% of the feruloylated material from both AIRs. Of the feruloyl esters solubilised from Festuca and Zea AIRs, 72 and 56% respectively were small enough to be mobile on paper chromatography. The major feruloylated product of Zea AIR was the known 5-O-feruloyl-alpha-L-Araf-(1-->3)-beta-D-Xylp-(1-->4)- D-Xyl (Fer-Ara-Xyl-Xyl). In contrast, the smallest major feruloylated product of Festuca AIR was a feruloyl pentasaccharide (3) containing 3 Xyl, 1 Ara and 1 non-pentose residue (NPR). The Ara and two of the three Xyl groups of 3 were resistant to NaIO4. Mild acid hydrolysis of 3 gave xylobiose, a feruloyl trisaccharide and beta-D-Xylp-(1-->2)-(5-O-feruloyl)-L-Ara. Compound 3 was therefore NPR-(1-->3)-beta-D-Xylp-(1-->2)-(5-O-feruloyl)-alpha-L-Ar af-(1-->3)-beta-D-Xylp-(1-->4)-D-Xyl. We conclude that the complex feruloyl oligosaccharide side-chains of Festuca arabinoxylan do not protect the polysaccharide against hydrolysis by the fungal glycanases present in Driselase.

Novel alanines bearing a heteroaromatic side chain: synthesis and studies on fluorescent chemosensing of metal cations with biological relevance.

PubMed

Ferreira, Rosa Cristina M; Raposo, Maria Manuela M; Costa, Susana P G

2018-06-01

A family of novel thienylbenzoxazol-5-yl-L-alanines, consisting of an alanine core bearing a benzoxazole at the side chain with a thiophene ring at position 2, substituted with different (hetero)aryl substituents, was synthesised to study the tuning of the photophysical and chemosensory properties of the resulting compounds. These novel heterocyclic alanines 3a-f and a series of structurally related bis-thienylbenzoxazolyl-alanines 3g-j were evaluated for the first time in the recognition of selected metal cations with environmental, medicinal and analytical interest such as Co 2+ , Cu 2+ , Zn 2+ and Ni 2+ , in acetonitrile solution, with the heterocycles at the side chain acting simultaneously as the coordinating and reporting units, via fluorescence changes. This behaviour can be explained by the involvement of the electron donor heteroatoms in the recognition event, through complexation of the metal cations. The spectrofluorimetric titrations showed that thienylbenzoxazolyl-alanines 3a-j and 4a,b were non-selective fluorimetric chemosensors for the above-mentioned cations, with the best results being obtained for the interaction of Cu 2+ with bis-alanine 3j and deprotected alanines 4a,b. The encouraging photophysical and metal ion sensing properties of these thienylbenzoxazolyl-alanines suggest that they can be used to obtain bioinspired fluorescent reporters for metal ion such as peptides/proteins with chemosensory/probing ability.

Symmetry Breaking in Side Chains Leading to Mixed Orientations and Improved Charge Transport in Isoindigo-alt-Bithiophene Based Polymer Thin Films.

PubMed

Xue, Guobiao; Zhao, Xikang; Qu, Ge; Xu, Tianbai; Gumyusenge, Aristide; Zhang, Zhuorui; Zhao, Yan; Diao, Ying; Li, Hanying; Mei, Jianguo

2017-08-02

The selection of side chains is important in design of conjugated polymers. It not only affects their intrinsic physical properties, but also has an impact on thin film morphologies. Recent reports suggested that a face-on/edge-on bimodal orientation observed in polymer thin films may be responsible for a three-dimensional (3D) charge transport and leads to dramatically improved mobility in donor-acceptor based conjugated polymers. To achieve a bimodal orientation in thin films has been seldom explored from the aspect of molecular design. Here, we demonstrate a design strategy involving the use of asymmetric side chains that enables an isoindigo-based polymer to adopt a distinct bimodal orientation, confirmed by the grazing incidence X-ray diffraction. As a result, the polymer presents an average high mobility of 3.8 ± 0.7 cm 2 V -1 s -1 with a maximum value of 5.1 cm 2 V -1 s -1 , in comparison with 0.47 and 0.51 cm 2 V -1 s -1 obtained from the two reference polymers. This study exemplifies a new strategy to develop the next generation polymers through understanding the property-structure relationship.

Symmetry Breaking in Side Chains Leading to Mixed Orientations and Improved Charge Transport in Isoindigo- alt -Bithiophene Based Polymer Thin Films

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

Xue, Guobiao; Zhao, Xikang; Qu, Ge

The selection of side chains is important in design of conjugated polymers. It not only affects their intrinsic physical properties, but also has an impact on thin film morphologies. Recent reports suggested that a face-on/edge-on bimodal orientation observed in polymer thin films may be responsible for a three-dimensional (3D) charge transport and leads to dramatically improved mobility in donor–acceptor based conjugated polymers. To achieve a bimodal orientation in thin films has been seldom explored from the aspect of molecular design. Here, we demonstrate a design strategy involving the use of asymmetric side chains that enables an isoindigo-based polymer to adoptmore » a distinct bimodal orientation, confirmed by the grazing incidence X-ray diffraction. As a result, the polymer presents an average high mobility of 3.8 ± 0.7 cm2 V–1 s–1 with a maximum value of 5.1 cm2 V–1 s–1, in comparison with 0.47 and 0.51 cm2 V–1 s–1 obtained from the two reference polymers. This study exemplifies a new strategy to develop the next generation polymers through understanding the property-structure relationship.« less

On the complex •OH/•O--induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain.

PubMed

Szabó, László; Mile, Viktória; Tóth, Tünde; Balogh, György T; Földes, Tamás; Takács, Erzsébet; Wojnárovits, László

2017-02-01

A full account of the • OH-induced free radical chemistry of an arylalkylamine is given taking all the possible reaction pathways quantitatively into consideration. Such knowledge is indispensable when the alkylamine side chain plays a crucial role in biological activity. The fundamental reactions are investigated on the model compound N-methyl-3-phenypropylamine (MPPA), and extended to its biologically active analog, to the antidepressant fluoxetine (FLX). Pulse radiolysis techniques were applied including redox titration and transient spectral analysis supplemented with DFT calculations. The contribution of the amine moiety to the free radical-induced oxidation mechanism appeared to be appreciable. • O - was used to observe hydrogen atom abstraction events at pH 14 giving rise to the strongly reducing α-aminoalkyl radicals (∼38% of the radical yield) and to benzyl (∼4%), β-aminoalkyl (∼24%), and aminyl radicals (∼31%) of MPPA. One-electron transfer was also observed yielding aminium radicals with low efficiency (∼3%). In the • OH-induced oxidation protonated α-aminoalkyl (∼49%), β-aminoalkyl (∼27%), benzyl radicals (∼4%), and aminium radicals (∼5%) are initially generated on the side chain of MPPA at pH 6, whereas hydroxycyclohexadienyl radicals (∼15%) were also produced. These initial events are followed by complex protonation-deprotonation reactions establishing acid-base equilibria; however, these processes are limited by the transient nature of the radicals and the kinetics of the ongoing reactions. The contribution of the radicals from the side chain alkylamine substituent of FLX totals up to ∼54% of the initially available oxidant yield.

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.

Development of side-chain NLO polymer materials with high electro-optic activity and long-term stability

NASA Astrophysics Data System (ADS)

Huang, Diyun; Parker, Timothy; Guan, Hann Wen; Cong, Shuxin; Jin, Danliang; Dinu, Raluca; Chen, Baoquan; Tolstedt, Don; Wolf, Nick; Condon, Stephen

2005-01-01

The electro-optic coefficient and long-term dipole alignment stability are two major factors in the development of high performance NLO materials for the application of high-speed EO devices. We have developed a high performance non-linear organic chromophore and incorporated it into a crosslinkable side-chain polyimide system. The polymer was synthesized through stepwise grafting of the crosslinker followed by the chromophore onto the polyimide backbone via esterification. Different chromophore loading levels were achieved by adjusting the crosslinker/chromophore feeding ratio. The polyimides films were contact-poled with second-harmonic generation monitoring. A large EO coefficient value was obtained and good long-term thermal stability at 85°C was observed.

In vitro and in vivo antimalarial activity of amphiphilic naphthothiazolium salts with amine-bearing side chains.

PubMed

Ulrich, Peter; Gipson, Gregory R; Clark, Martha A; Tripathi, Abhai; Sullivan, David J; Cerami, Carla

2014-10-01

Because of emerging resistance to existing drugs, new chemical classes of antimalarial drugs are urgently needed. We have rationally designed a library of compounds that were predicted to accumulate in the digestive vacuole and then decrystallize hemozoin by breaking the iron carboxylate bond in hemozoin. We report the synthesis of 16 naphthothiazolium salts with amine-bearing side chains and their activities against the erythrocytic stage of Plasmodium falciparum in vitro. KSWI-855, the compound with the highest efficacy against the asexual stages of P. falciparum in vitro, also had in vitro activity against P. falciparum gametocytes and in vivo activity against P. berghei in a murine malaria model. © The American Society of Tropical Medicine and Hygiene.

Effects of Xylan Side-Chain Substitutions on Xylan-Cellulose Interactions and Implications for Thermal Pretreatment of Cellulosic Biomass.

PubMed

Pereira, Caroline S; Silveira, Rodrigo L; Dupree, Paul; Skaf, Munir S

2017-04-10

Lignocellulosic biomass is mainly constituted by cellulose, hemicellulose, and lignin and represents an important resource for the sustainable production of biofuels and green chemistry materials. Xylans, a common hemicellulose, interact with cellulose and often exhibit various side chain substitutions including acetate, (4-O-methyl) glucuronic acid, and arabinose. Recent studies have shown that the distribution of xylan substitutions is not random, but follows patterns that are dependent on the plant taxonomic family and cell wall type. Here, we use molecular dynamics simulations to investigate the role of substitutions on xylan interactions with the hydrophilic cellulose face, using the recently discovered xylan decoration pattern of the conifer gymnosperms as a model. The results show that α-1,2-linked substitutions stabilize the binding of single xylan chains independently of the nature of the substitution and that Ca 2+ ions can mediate cross-links between glucuronic acid substitutions of two neighboring xylan chains, thus stabilizing binding. At high temperature, xylans move from the hydrophilic to the hydrophobic cellulose surface and are also stabilized by Ca 2+ cross-links. Our results help to explain the role of substitutions on xylan-cellulose interactions, and improve our understanding of the plant cell wall architecture and the fundamentals of biomass pretreatments.

Chemoenzymatic synthesis of statine side chain building blocks and application in the total synthesis of the cholesterol-lowering compound solistatin.

PubMed

Rieder, Oliver; Wolberg, Michael; Foegen, Silke E; Müller, Michael

2017-09-20

The synthesis and enzymatic reduction of several 6-substituted dioxohexanoates are presented. Two-step syntheses of tert-butyl 6-bromo-3,5-dioxohexanoate and the corresponding 6-hydroxy compound have been achieved in 89% and 59% yield, respectively. Regio- and enantioselective reduction of these diketones and of the 6-chloro derivative with alcohol dehydrogenase from Lactobacillus brevis (LBADH) gave the (5S)-5-hydroxy-3-oxo products with enantiomeric excesses of 91%, 98.4%, and >99.5%, respectively. Chain elongation of the reduction products by one carbon via cyanide addition, and by more than one carbon by Julia-Kocienski olefination, gave access to well-established statine side-chain building blocks. Application in the synthesis of the cholesterol-lowering natural compound solistatin is given. Copyright © 2017 Elsevier B.V. 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.

Smectic order and backbone anisotropy of a side-chain liquid crystalline polymer by Small-Angle Neutron Scattering

NASA Astrophysics Data System (ADS)

Noirez, L.; Pépy, G.; Keller, P.; Benguigui, L.

1991-07-01

We have simultaneously measured, for the first time, the extension of the polymer backbone of a side-chain liquid crystalline polymer and the intensity of the 001 Bragg reflection, which gives the smectic order parameter Psi as a function of temperature in the smectic phase. We have qualitatively demonstrated that the more the smectic phase is ordered, the more the polymer backbone is localized between the mesogenic layers. It is shown that the Landau theory allows us to relate the radius of gyration parallel to the magnetic field of the polymer backbone to the smectic order parameter. We also show that the Renz-Warner theory is suitable at low temperatures.

A novel α-galactosidase from Fusarium oxysporum and its application in determining the structure of the gum arabic side chain.

PubMed

Maruta, Akiho; Yamane, Mirei; Matsubara, Midori; Suzuki, Shiho; Nakazawa, Masami; Ueda, Mitsuhiro; Sakamoto, Tatsuji

2017-08-01

We previously reported that Fusarium oxysporum 12S produces two bifunctional proteins, FoAP1 and FoAP2, with α-d-galactopyranosidase (GPase) and β-l-arabinopyranosidase (APase) activities. The aim of this paper was to purify a third GPase, FoGP1, from culture supernatant of F. oxysporum 12S, to characterize it, and to determine its mode of action towards gum arabic. A cDNA encoding FoGP1 was cloned and the protein was overexpressed in Escherichia coli. Module sequence analysis revealed the presence of a GH27 domain in FoGP1. The recombinant enzyme (rFoGP1) showed a GPase/APase activity ratio of 330, which was quite different from that of FoAP1 (1.7) and FoAP2 (0.2). Among the natural substrates tested, rFoGP1 showed the highest activity towards gum arabic. In contrast to other well-characterized GPases, rFoGP1 released a small amount of galactose from α-galactosyl oligosaccharides such as raffinose and exhibited no activity toward galactomannans, which are highly substituted with α-galactosyl side chains. This indicated that FoGP1 is an unusual type of GPase. rFoGP1 released 30% of the total galactose from gum arabic, suggesting the existence of a large number of α-galactosyl residues at the non-reducing ends of gum arabic side chains. Together, rFoGP1 and α-l-arabinofuranosidase released four times more arabinose than α-l-arabinofuranosidase acting alone. This suggested that a large number of α-l-arabinofuranosyl residues is capped by α-galactosyl residues. 1 H NMR experiments revealed that rFoGP1 hydrolyzed the α-1,3-galactosidic linkage within the side chain structure of [α-d-Galp-(1→3)-α-l-Araf-(1→] in gum arabic. In conclusion, rFoGP1 is highly active toward α-1,3-galactosyl linkages but negligibly or not active toward α-1,6-galactosyl linkages. The novel FoGP1 might be used to modify the physical properties of gum arabic, which is an industrially important polysaccharide used as an emulsion stabilizer and coating agent. Copyright © 2017

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.

Surface Engineering of ITO Substrates to Improve the Memory Performance of an Asymmetric Conjugated Molecule with a Side Chain.

PubMed

Hou, Xiang; Cheng, Xue-Feng; Xiao, Xin; He, Jing-Hui; Xu, Qing-Feng; Li, Hua; Li, Na-Jun; Chen, Dong-Yun; Lu, Jian-Mei

2017-09-05

Organic multilevel random resistive access memory (RRAM) devices with an electrode/organic layer/electrode sandwich-like structure suffer from poor reproducibility, such as low effective ternary device yields and a wide threshold voltage distribution, and improvements through organic material renovation are rather limited. In contrast, engineering of the electrode surfaces rather than molecule design has been demonstrated to boost the performance of organic electronics effectively. Herein, we introduce surface engineering into organic multilevel RRAMs to enhance their ternary memory performance. A new asymmetric conjugated molecule composed of phenothiazine and malononitrile with a side chain (PTZ-PTZO-CN) was fabricated in an indium tin oxide (ITO)/PTZ-PTZO-CN/Al sandwich-like memory device. Modification of the ITO substrate with a phosphonic acid (PA) prior to device fabrication increased the ternary device yield (the ratio of effective ternary device) and narrowed the threshold voltage distribution. The crystallinity analysis revealed that PTZ-PTZO-CN grown on untreated ITO crystallized into two phases. After the surface engineering of ITO, this crystalline ambiguity was eliminated and a sole crystal phase was obtained that was the same as in the powder state. The unified crystal structure and improved grain mosaicity resulted in a lower threshold voltage and, therefore, a higher ternary device yield. Our result demonstrated that PA modification also improved the memory performance of an asymmetric conjugated molecule with a side chain. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Amino Acid Selective 13C Labeling and 13C Scrambling Profile Analysis of Protein α and Side-Chain Carbons in Escherichia coli Utilized for Protein Nuclear Magnetic Resonance.

PubMed

Sugiki, Toshihiko; Furuita, Kyoko; Fujiwara, Toshimichi; Kojima, Chojiro

2018-06-20

Amino acid selective isotope labeling is an important nuclear magnetic resonance technique, especially for larger proteins, providing strong bases for the unambiguous resonance assignments and information concerning the structure, dynamics, and intermolecular interactions. Amino acid selective 15 N labeling suffers from isotope dilution caused by metabolic interconversion of the amino acids, resulting in isotope scrambling within the target protein. Carbonyl 13 C atoms experience less isotope scrambling than the main-chain 15 N atoms do. However, little is known about the side-chain 13 C atoms. Here, the 13 C scrambling profiles of the Cα and side-chain carbons were investigated for 15 N scrambling-prone amino acids, such as Leu, Ile, Tyr, Phe, Thr, Val, and Ala. The level of isotope scrambling was substantially lower in 13 Cα and 13 C side-chain labeling than in 15 N labeling. We utilized this reduced scrambling-prone character of 13 C as a simple and efficient method for amino acid selective 13 C labeling using an Escherichia coli cold-shock expression system and high-cell density fermentation. Using this method, the 13 C labeling efficiency was >80% for Leu and Ile, ∼60% for Tyr and Phe, ∼50% for Thr, ∼40% for Val, and 30-40% for Ala. 1 H- 15 N heteronuclear single-quantum coherence signals of the 15 N scrambling-prone amino acid were also easily filtered using 15 N-{ 13 Cα} spin-echo difference experiments. Our method could be applied to the assignment of the 55 kDa protein.

Validation of molecularly imprinted polymers for side chain selective phosphopeptide enrichment.

PubMed

Chen, Jing; Shinde, Sudhirkumar; Subedi, Prabal; Wierzbicka, Celina; Sellergren, Börje; Helling, Stefan; Marcus, Katrin

2016-11-04

Selective enrichment techniques are essential for mapping of protein posttranslational modifications (PTMs). Phosphorylation is one of the PTMs which continues to be associated with significant analytical challenges. Particularly problematic are tyrosine-phosphorylated peptides (pY-peptides) resulting from tryptic digestion which commonly escape current chemo- or immuno- affinity enrichments and hence remain undetected. We here report on significant improvements in this regard using pY selective molecularly imprinted polymers (pY-MIPs). The pY-MIP was compared with titanium dioxide (TiO 2 ) affinity based enrichment and immunoprecipitation (IP) with respect to selective enrichment from a mixture of 13 standard peptides at different sample loads. At a low sample load (1pmol of each peptide), IP resulted in enrichment of only a triply phosphorylated peptide whereas TiO 2 enriched phosphopeptides irrespective of the amino acid side chain. However, with increased sample complexity, TiO 2 failed to enrich the doubly phosphorylated peptides. This contrasted with the pY-MIP showing enrichment of all four tyrosine phosphorylated peptides at 1pmol sample load of each peptide with a few other peptides binding unselectively. At an increased sample complexity consisting of the standard peptides spiked into mouse brain digest, the MIP showed clear enrichment of all four pY- peptides. Copyright © 2016 Elsevier B.V. All rights reserved.

Side-Chain Liquid Crystalline Poly(meth)acrylates with Bent-Core Mesogens

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

Chen,X.; Tenneti, K.; Li, C.

2007-01-01

We report the design, synthesis, and characterization of side-chain liquid crystalline (LC) poly(meth)acrylates with end-on bent-core liquid crystalline (BCLC) mesogens. Both conventional free radical polymerization and atom transfer radical polymerization have been used to synthesize these liquid crystalline polymers (LCP). The resulting polymers exhibit thermotropic LC behavior. Differential scanning calorimetry, thermopolarized light microscopy, wide-angle X-ray diffraction, and small-angle X-ray scattering were used to characterize the LC structure of both monomers and polymers. The electro-optic (EO) measurement was carried out by applying a triangular wave and measuring the LC EO response. SmCP (Smectic C indicates the LC molecules are tilted withmore » respect to the layer normal; P denotes polar ordering) phases were observed for both monomers and polymers. In LC monomers, typical antiferroelectric switching was observed. In the ground state, SmCP{sub A} (A denotes antiferroelectric) was observed which switched to SmCP{sub F} (F denotes ferroelectric) upon applying an electric field. In the corresponding LCP, a unique bilayer structure was observed, which is different from the reported BCLC bilayer SmCG (G denotes generated) phase. Most of the LCPs did not switch upon applying electric field while weak AF switching was observed in a low molecular weight poly{l_brace}3'-[4-(4-n-dodecyloxybenzoyloxy)benzoyloxy]-4-(12-acryloyloxydodecyloxy)benzoyloxybiphenyl{r_brace} sample.« less

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.

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.

Differentiating Amino Acid Residues and Side Chain Orientations in Peptides Using Scanning Tunneling Microscopy

PubMed Central

Claridge, Shelley A.; Thomas, John C.; Silverman, Miles A.; Schwartz, Jeffrey J.; Yang, Yanlian; Wang, Chen; Weiss, Paul S.

2014-01-01

Single-molecule measurements of complex biological structures such as proteins are an attractive route for determining structures of the large number of important biomolecules that have proved refractory to analysis through standard techniques such as X-ray crystallography and nuclear magnetic resonance. We use a custom-built low-current scanning tunneling microscope to image peptide structure at the single-molecule scale in a model peptide that forms β sheets, a structural motif common in protein misfolding diseases. We successfully differentiate between histidine and alanine amino acid residues, and further differentiate side chain orientations in individual histidine residues, by correlating features in scanning tunneling microscope images with those in energy-optimized models. Beta sheets containing histidine residues are used as a model system due to the role histidine plays in transition metal binding associated with amyloid oligomerization in Alzheimer’s and other diseases. Such measurements are a first step toward analyzing peptide and protein structures at the single-molecule level. PMID:24219245

The influence of the side-chain sequence on the structure-activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides.

PubMed

Mezö, G; Hudecz, F; Kajtár, J; Szókán, G; Szekerke, M

1989-10-01

New branched polypeptides were synthesized for a detailed study of the influence of the side-chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L-Lys]. These polymers contain either DL-Ala3-X [poly[Lys-(X-DL-Ala3)n

Rapid assessment of oxidation via middle-down LCMS correlates with methionine side-chain solvent-accessible surface area for 121 clinical stage monoclonal antibodies.

PubMed

Yang, Rong; Jain, Tushar; Lynaugh, Heather; Nobrega, R Paul; Lu, Xiaojun; Boland, Todd; Burnina, Irina; Sun, Tingwan; Caffry, Isabelle; Brown, Michael; Zhi, Xiaoyong; Lilov, Asparouh; Xu, Yingda

Susceptibility of methionine to oxidation is an important concern for chemical stability during the development of a monoclonal antibody (mAb) therapeutic. To minimize downstream risks, leading candidates are usually screened under forced oxidation conditions to identify oxidation-labile molecules. Here we report results of forced oxidation on a large set of in-house expressed and purified mAbs with variable region sequences corresponding to 121 clinical stage mAbs. These mAb samples were treated with 0.1% H 2 O 2 for 24 hours before enzymatic cleavage below the hinge, followed by reduction of inter-chain disulfide bonds for the detection of the light chain, Fab portion of heavy chain (Fd) and Fc by liquid chromatography-mass spectrometry. This high-throughput, middle-down approach allows detection of oxidation site(s) at the resolution of 3 distinct segments. The experimental oxidation data correlates well with theoretical predictions based on the solvent-accessible surface area of the methionine side-chains within these segments. These results validate the use of upstream computational modeling to predict mAb oxidation susceptibility at the sequence level.

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

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection.

PubMed

Uppu, Divakara S S M; Samaddar, Sandip; Ghosh, Chandradhish; Paramanandham, Krishnamoorthy; Shome, Bibek R; Haldar, Jayanta

2016-01-01

Bacterial biofilms represent the root-cause of chronic or persistent infections in humans. Gram-negative bacterial infections due to nosocomial and opportunistic pathogens such as Acinetobacter baumannii are more difficult to treat because of their inherent and rapidly acquiring resistance to antibiotics. Due to biofilm formation, A. baumannii has been noted for its apparent ability to survive on artificial surfaces for an extended period of time, therefore allowing it to persist in the hospital environment. Here we report, maleic anhydride based novel cationic polymers appended with amide side chains that disrupt surface established multi-drug resistant A. baumannii biofilms. More importantly, these polymers significantly (p < 0.0001) decrease the bacterial burden in mice with chronic A. baumannii burn wound infection. The polymers also show potent antibacterial efficacy against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococci (VRE) and multi-drug resistant clinical isolates of A. baumannii with minimal toxicity to mammalian cells. We observe that optimal hydrophobicity dependent on the side chain chemical structure of these polymers dictate the selective toxicity to bacteria. Polymers interact with the bacterial cell membranes by causing membrane depolarization, permeabilization and energy depletion. Bacteria develop rapid resistance to erythromycin and colistin whereas no detectable development of resistance occurs against these polymers even after several passages. These results suggest the potential use of these polymeric biomaterials in disinfecting biomedical device surfaces after the infection has become established and also for the topical treatment of chronic bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

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.

Oxidative cleavage of the octyl side chain of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045) in rat and dog liver preparations.

PubMed

Umehara, K; Kudo, S; Hirao, Y; Morita, S; Uchida, M; Odomi, M; Miyamoto, G

2000-08-01

The metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a new potent biguanide antiseptic, was investigated using rat and dog liver preparations to elucidate the mechanism of OPB-2045 metabolite formation, in which the octyl side chain is reduced to four, five, or six carbon atoms. Chemical structures of metabolites were characterized by 1H NMR, fast atom bombardment/mass spectrometry, and liquid chromatography/electrospray ionization-tandem mass spectrometry. Three main metabolites were observed during incubation of OPB-2045 with rat liver S9: 2-octanol (M-1), 3-octanol (M-2), and 4-octanol (M-3). In the incubation of OPB-2045 with dog liver S9, eight metabolites were observed, seven of which being M-1, M-2, M-3, 2-octanone (M-4), threo-2,3-octandiol (M-5), erythro-2,3-octandiol (M-6), and 1,2-octandiol (M-7). M-5 and M-6 were further biotransformed to a ketol derivative and C-C bond cleavage metabolite (hexanoic acid derivative), an in vivo end product, in the incubation with dog liver microsomes. The reactions required NADPH as a cofactor and were significantly inhibited by the various inhibitors of cytochrome P450 (i.e., CO, n-octylamine, SKF 525-A, metyrapone, and alpha-naphthoflavone). The results indicate that the degraded products of OPB-2045 are produced by C-C bond cleavage after monohydroxylation, dihydroxylation, and ketol formation at the site of the octyl side chain with possible involvement of cytochrome P450 systems. This aliphatic C-C bond cleavage by sequential oxidative reactions may play an important role in the metabolism of other drugs or endogenous compounds that possess aliphatic chains.

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.

Light-induced yellowing of selectively 13C-enriched dehydrogenation polymers (DHPs). Part 1, Side-chain 13C-enriched DHP ([alpha], [beta], and [gamma]-13C)

Treesearch

Jim Parkas; Magnus Paulsson; Terashima Noritsugu; Ulla Westermark; Sally Ralph

2004-01-01

Light-induced yellowing has been studied using side-chain ([alpha], [beta], and [gamma]) 13C-enriched DHP (dehydrogenation polymer) and quantitative solution state 13C NMR spectroscopy. The DHP was formed from 13C-enriched coniferin using an enzymatic system consisting of [beta]-glucosidase, glucose oxidase, and peroxidase in a pH 6 buffer solution. The DHP was applied...

Hydrogen Bond Switching among Flavin and Amino Acid Side Chains in the BLUF Photoreceptor Observed by Ultrafast Infrared Spectroscopy

PubMed Central

Bonetti, Cosimo; Mathes, Tilo; van Stokkum, Ivo H. M.; Mullen, Katharine M.; Groot, Marie-Louise; van Grondelle, Rienk; Hegemann, Peter; Kennis, John T. M.

2008-01-01

BLUF domains constitute a recently discovered class of photoreceptor proteins found in bacteria and eukaryotic algae. BLUF domains are blue-light sensitive through a FAD cofactor that is involved in an extensive hydrogen-bond network with nearby amino acid side chains, including a highly conserved tyrosine and glutamine. The participation of particular amino acid side chains in the ultrafast hydrogen-bond switching reaction with FAD that underlies photoactivation of BLUF domains is assessed by means of ultrafast infrared spectroscopy. Blue-light absorption by FAD results in formation of FAD•− and a bleach of the tyrosine ring vibrational mode on a picosecond timescale, showing that electron transfer from tyrosine to FAD constitutes the primary photochemistry. This interpretation is supported by the absence of a kinetic isotope effect on the fluorescence decay on H/D exchange. Subsequent protonation of FAD•− to result in FADH• on a picosecond timescale is evidenced by the appearance of a N-H bending mode at the FAD N5 protonation site and of a FADH• C=N stretch marker mode, with tyrosine as the likely proton donor. FADH• is reoxidized in 67 ps (180 ps in D2O) to result in a long-lived hydrogen-bond switched network around FAD. This hydrogen-bond switch shows infrared signatures from the C-OH stretch of tyrosine and the FAD C4=O and C=N stretches, which indicate increased hydrogen-bond strength at all these sites. The results support a previously hypothesized rotation of glutamine by ∼180° through a light-driven radical-pair mechanism as the determinant of the hydrogen-bond switch. PMID:18708458

Subcompartment localization of the side chain xyloglucan-synthesizing enzymes within Golgi stacks of tobacco suspension-cultured cells.

PubMed

Chevalier, Laurence; Bernard, Sophie; Ramdani, Yasmina; Lamour, Romain; Bardor, Muriel; Lerouge, Patrice; Follet-Gueye, Marie-Laure; Driouich, Azeddine

2010-12-01

Xyloglucan is the dominant hemicellulosic polysaccharide of the primary cell wall of dicotyledonous plants that plays a key role in plant development. It is well established that xyloglucan is assembled within Golgi stacks and transported in Golgi-derived vesicles to the cell wall. It is also known that the biosynthesis of xyloglucan requires the action of glycosyltransferases including α-1,6-xylosyltransferase, β-1,2-galactosyltransferase and α-1,2-fucosyltransferase activities responsible for the addition of xylose, galactose and fucose residues to the side chains. There is, however, a lack of knowledge on how these enzymes are distributed within subcompartments of Golgi stacks. We have undertaken a study aiming at mapping these glycosyltransferases within Golgi stacks using immunogold-electron microscopy. To this end, we generated transgenic lines of tobacco (Nicotiana tabacum) BY-2 suspension-cultured cells expressing either the α-1,6-xylosyltransferase, AtXT1, the β-1,2-galactosyltransferase, AtMUR3, or the α-1,2-fucosyltransferase AtFUT1 of Arabidopsis thaliana fused to green-fluorescent protein (GFP). Localization of the fusion proteins within the endomembrane system was assessed using confocal microscopy. Additionally, tobacco cells were high pressure-frozen/freeze-substituted and subjected to quantitative immunogold labelling using anti-GFP antibodies to determine the localization patterns of the enzymes within subtypes of Golgi cisternae. The data demonstrate that: (i) all fusion proteins, AtXT1-GFP, AtMUR3-GFP and AtFUT1-GFP are specifically targeted to the Golgi apparatus; and (ii) AtXT1-GFP is mainly located in the cis and medial cisternae, AtMUR3-GFP is predominantly associated with medial cisternae and AtFUT1-GFP mostly detected over trans cisternae suggesting that initiation of xyloglucan side chains occurs in early Golgi compartments in tobacco cells. The Plant Journal © 2010 Blackwell Publishing Ltd. No claim to original US government works.

Dynamic properties of the native free antithrombin from molecular dynamics simulations: computational evidence for solvent- exposed Arg393 side chain.

PubMed

Tóth, László; Fekete, Attila; Balogh, Gábor; Bereczky, Zsuzsanna; Komáromi, István

2015-09-01

While antithrombin (AT) has small basal inhibitory activity, it reaches its full inhibitory potential against activated blood coagulation factors, FXa, FIXa, and FIIa (thrombin), via an allosteric and/or template (bridging) mechanism by the action of heparin, heparan sulfate, or heparin-mimetic pentasaccharides (PS). From the numerous X-ray structures available for different conformational states of AT, only indirect and incomplete conclusions can be drawn on the inherently dynamic properties of AT. As a typical example, the basal inhibitory activity of AT cannot be interpreted on the basis of "non-activated" free antithrombin X-ray structures since the Arg393 side chain, playing crucial role in antithrombin-proteinase interaction, is not exposed. In order to reveal the intrinsic dynamic properties and the reason of basal inhibitory activity of antithrombin, 2 μs molecular dynamics simulations were carried out on its native free-forms. It was shown from the simulation trajectories that the reactive center loop which is functioning as "bait" for proteases, even without any biasing potential can populate conformational state in which the Arg393 side chain is solvent exposed. It is revealed from the trajectory analysis that the peptide sequences correspond to the helix D extension, and new helix P formation can be featured with especially large root-mean-square fluctuations. Mutual information analyses of the trajectory showed remarkable (generalized) correlation between those regions of antithrombin which changed their conformations as the consequence of AT-PS complex formation. This suggests that allosteric information propagation pathways are present even in the non-activated native form of AT.

Evidence for side-chain π-delocalization in a planar substituted benzene: an experimental and theoretical charge density study on 2,5-dimethoxybenzaldehyde thiosemicarbazone.

PubMed

Farrugia, Louis J; Khalaji, Aliakbar Dehno

2011-11-17

The charge density in 2,5-dimethoxybenzaldehyde thiosemicarbazone (1) has been studied experimentally using Mo-K(α) X-ray diffraction at 100 K, and by theory using DFT calculations at the B3LYP/6-311++G(2d,2p) level. The quantum theory of atoms in molecules (QTAIM) was used to investigate the extent of π-delocalization in the thioamide side-chain, which is virtually coplanar with the benzene ring. The experimental and theoretical ellipticity profiles along the bond paths were in excellent agreement, and showed that some of the formal single bonds in the side-chain have significant π-bond character. This view was supported by the magnitudes of the topological bond orders and by the delocalization indices δ(Ω(A), Ω(B)). An orbital decomposition of δ(Ω(A), Ω(B)) demonstrated that there was significant π-character in all the interchain non-H chemical bonds. On the other hand, the source function referenced at the interchain bond critical points could not provide any evidence for π-delocalization, showing instead only limited σ-delocalization between nearest neighbors. Overall, the topological evidence and the atomic graphs of the oxygen atoms did not provide convincing evidence for π-delocalization involving the methoxy substituents.

Thermoresponsive Polyurethane Bearing Oligo(Ethylene Glycol) as Side Chain Without Polyol at Polymer Backbone Achieved Excellent Hydrophilic and Hydrophobic Switching.

PubMed

Aoki, Daisuke; Ajiro, Hiroharu

2018-06-13

In order to prepare thermoresponsive polyurethane gels, a novel polyurethane bearing oligo(ethylene glycol) (OEG) as the side chain is successfully synthesized with hexamethylene diisocyanate and OEG tartrate ester. The aqueous solution of the polyurethane shows sharp and clear lower critical solution temperature behavior at 34 °C. Furthermore, a hydrogel based on the same polyurethane is also successfully prepared using glycerol as the crosslinker. This polyurethane hydrogel including 10 mol% of glycerol presents a large swelling ratio change between 4 °C and 37 °C from 250% to 40%. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Studies on the O-polysaccharide of Escherichia albertii O2 characterized by non-stoichiometric O-acetylation and non-stoichiometric side-chain l-fucosylation.

PubMed

Naumenko, Olesya I; Zheng, Han; Xiong, Yanwen; Senchenkova, Sof'ya N; Wang, Hong; Shashkov, Alexander S; Li, Qun; Wang, Jianping; Knirel, Yuriy A

2018-05-22

An O-polysaccharide was isolated from the lipopolysaccharide of Escherichia albertii O2 and studied by chemical methods and 1D and 2D 1 H and 13 C NMR spectroscopy. The following structure of the O-polysaccharide was established: . The O-polysaccharide is characterized by masked regularity owing to a non-stoichiometric O-acetylation of an l-fucose residue in the main chain and a non-stoichiometric side-chain l-fucosylation of a β-GlcNAc residue. A regular linear polysaccharide was obtained by sequential Smith degradation and alkaline O-deacetylation of the O-polysaccharide. The content of the O-antigen gene cluster of E. albertii O2 was found to be essentially consistent with the O-polysaccharide structure established. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of side-chain substitution and hot processing on diketopyrrolopyrrole-based polymers for organic solar cells.

PubMed

Heintges, Gaël H L; Leenaers, Pieter J; Janssen, René A J

2017-07-14

The effects of cold and hot processing on the performance of polymer-fullerene solar cells are investigated for diketopyrrolopyrrole (DPP) based polymers that were specifically designed and synthesized to exhibit a strong temperature-dependent aggregation in solution. The polymers, consisting of alternating DPP and oligothiophene units, are substituted with linear and second position branched alkyl side chains. For the polymer-fullerene blends that can be processed at room temperature, hot processing does not enhance the power conversion efficiencies compared to cold processing because the increased solubility at elevated temperatures results in the formation of wider polymer fibres that reduce charge generation. Instead, hot processing seems to be advantageous when cold processing is not possible due to a limited solubility at room temperature. The resulting morphologies are consistent with a nucleation-growth mechanism for polymer fibres during drying of the films.

Backbone and stereospecific (13)C methyl Ile (δ1), Leu and Val side-chain chemical shift assignments of Crc.

PubMed

Sharma, Rakhi; Sahu, Bhubanananda; Ray, Malay K; Deshmukh, Mandar V

2015-04-01

Carbon catabolite repression (CCR) allows bacteria to selectively assimilate a preferred compound among a mixture of several potential carbon sources, thus boosting growth and economizing the cost of adaptability to variable nutrients in the environment. The RNA-binding catabolite repression control (Crc) protein acts as a global post-transcriptional regulator of CCR in Pseudomonas species. Crc triggers repression by inhibiting the expression of genes involved in transport and catabolism of non-preferred substrates, thus indirectly favoring assimilation of preferred one. We report here a nearly complete backbone and stereospecific (13)C methyl side-chain chemical shift assignments of Ile (δ1), Leu and Val of Crc (~ 31 kDa) from Pseudomonas syringae Lz4W.

The role of side chain conformational flexibility in surface recognition by Tenebrio molitor antifreeze protein

PubMed Central

Daley, Margaret E.; Sykes, Brian D.

2003-01-01

Two-dimensional nuclear magnetic resonance spectroscopy was used to investigate the flexibility of the threonine side chains in the β-helical Tenebrio molitor antifreeze protein (TmAFP) at low temperatures. From measurement of the 3Jαβ 1H-1H scalar coupling constants, the χ1 angles and preferred rotamer populations can be calculated. It was determined that the threonines on the ice-binding face of the protein adopt a preferred rotameric conformation at near freezing temperatures, whereas the threonines not on the ice-binding face sample many rotameric states. This suggests that TmAFP maintains a preformed ice-binding conformation in solution, wherein the rigid array of threonines that form the AFP-ice interface matches the ice crystal lattice. A key factor in binding to the ice surface and inhibition of ice crystal growth appears to be the close surface-to-surface complementarity between the AFP and crystalline ice, and the lack of an entropic penalty associated with freezing out motions in a flexible ligand. PMID:12824479

Backbone conformations and side chain flexibility of two somatostatin mimics investigated by molecular dynamics simulations.

PubMed

Interlandi, Gianluca

2009-05-15

Molecular dynamics simulations with two designed somatostatin mimics, SOM230 and SMS 201-995, were performed in explicit water for a total aggregated time of 208 ns. Analysis of the runs with SOM230 revealed the presence of two clusters of conformations. Strikingly, the two sampled conformers correspond to the two main X-ray structures in the asymmetric unit of SMS 201-995. Structural comparison between the residues of SOM230 and SMS 201-995 provides an explanation for the high binding affinity of SOM230 to four of five somatostatin receptors. Similarly, cluster analysis of the simulations with SMS 201-995 shows that the backbone of the peptide interconverts between its two main crystallographic conformers. The conformations of SMS 201-995 sampled in the two clusters violated two different sets of NOE distance constraints in agreement with a previous NMR study. Differences in side chain fluctuations between SOM230 and SMS 201-995 observed in the simulations may contribute to the relatively higher binding affinity of SOM230 to most somatostatin receptors.

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.

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.

5. EXTERIOR OF SOUTH SIDE SHOWING ELECTRICAL JUNCTION BOX NEXT ...

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

5. EXTERIOR OF SOUTH SIDE SHOWING ELECTRICAL JUNCTION BOX NEXT TO SOUTH SIDE DOOR AND CHAIN-LINK FENCE AROUND GARDEN AREA AT REAR OF HOUSE. VIEW TO NORTHWEST. - Bishop Creek Hydroelectric System, Plant 4, Worker Cottage, Bishop Creek, Bishop, Inyo County, CA

Hydrogen-bonded side chain liquid crystalline block copolymer: Molecular design, synthesis, characterization and applications

NASA Astrophysics Data System (ADS)

Chao, Chi-Yang

Block copolymers can self-assemble into highly regular, microphase-separated morphologies with dimensions at nanometer length scales. Potential applications such as optical wavelength photonic crystals, templates for nanolithographic patterning, or nanochannels for biomacromolecular separation take advantage of the well-ordered, controlled size microdomains of block copolymers. Side-chain liquid crystalline block copolymers (SCLCBCPs) are drawing increasing attention since the incorporation of liquid crystallinity turns their well-organized microstructures into dynamic functional materials. As a special type of block copolymer, hydrogen-bonded SCLCBCPs are unique, compositionally tunable materials with multiple dynamic functionalities that can readily respond to thermal, electrical and mechanical fields. Hydrogen-bonded SCLCBCPs were synthesized and assembled from host poly(styrene- b-acrylic acid) diblock copolymers with narrow molecular weight distributions as proton donors and guest imidazole functionalized mesogenic moieties as proton acceptors. In these studies non-covalent hydrogen bonding is employed to connect mesogenic side groups to a block copolymer backbone, both for its dynamic character as well as for facile materials preparation. The homogeneity and configuration of the hydrogen-bonded complexes were determined by both the molecular architecture of imidazolyl side groups and the process conditions. A one-dimensional photonic crystal composed of high molecular weight hydrogen-bonded SCLCBCP, with temperature dependent optical wavelength stop bands was successfully produced. The microstructures of hydrogen-bonded complexes could be rapidly aligned in an AC electric field at temperatures below the order-disorder transition but above their glass transitions. Remarkable dipolar properties of the mesogenic groups and thermal dissociation of hydrogen bonds are key elements to fast orientation switching. Studies of a wide range of mesogen and polymer

Teaching Spatial Awareness In Small-Sided Games

ERIC Educational Resources Information Center

Phillips, David; Hannon, James C.; Molina, Sergio

2015-01-01

This article supports the use of strategy and tactics at games stage three (how to teach basic offensive and defensive strategy using small-sided games) as a best practices in physical education. Potential learning through game stages three and four (full-sided games) is only possible when teachers have advanced content knowledge to teach the…

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

Kerr effect in the isotropic phase of a side-chain polymeric liquid crystal

NASA Astrophysics Data System (ADS)

Reys, V.; Dormoy, Y.; Collin, D.; Keller, P.; Martinoty, P.

1992-02-01

The birefringence induced by a pulsed electrical field was used to study the pretransitional effects associated with the isotropic phase of a side-chain polysiloxane. The results obtained show that these effects are characterised by a conventional value of the static exponent and an abnormal value of the dynamic exponent, which shows that the dynamic theory of low molecular weight liquid crystals does not apply. The results also reveal competition between the dipolar moments induced by the electrical field and the permanent moments of the mesogenic molecules. La biréfringence induite par un champ électrique impulsionnel a été utilisée pour étudier les effets prétransitionnels associés à la phase isotrope d'un polysiloxane à chaînes latérales. Les résultats obtenus montrent que ces effets sont caractérisés par une valeur classique de l'exposant statique et une valeur anormale de l'exposant dynamique. Ce dernier résultat montre que la théorie dynamique des cristaux liquides de bas poids moléculaire n'est pas applicable au cas présent. Les expériences mettent également en évidence une compétition entre les moments dipolaires induits par le champ électrique et les moments permanents des molécules mésogènes.

Synthesis, characterization, conformation and self-assembly behavior of polypeptide-based brush with oligo (ethylene glycol) side chains

NASA Astrophysics Data System (ADS)

Huang, Yugang; Luo, Weiang; Ye, Guodong

2015-02-01

A new polypeptide-based copolymer brush composed of poly (γ-propargyl-L-glutamate)-block-poly (propylene oxide)-block-poly (γ-propargyl-L-glutamate) backbone (PPLG-b-PPO-b-PPLG) and oligo (ethylene glycol) (PEG) side-chain was synthesized by combination of N-carboxyanhydride ring-opening polymerization and click chemistry. Nearly 100% grafting efficiency was achieved by copper-catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition (CuAAc) reaction. The α-helical conformation adopted by the grafted polypeptide blocks in water was relatively stable and showed a reversible change in a heating-cooling circle from 5 to 70 °C. It displayed weak stability against elevated temperature but still reversible changes in the presence of 0.47 M NaCl. The brushes were amphiphilic and could self-assemble into thermo-sensitive micelles in water. Big micelles could break into small micelles upon heating due to the improved solubility.

Role of Loop-Clamping Side Chains in Catalysis by Triosephosphate Isomerase.

PubMed

Zhai, Xiang; Amyes, Tina L; Richard, John P

2015-12-09

The side chains of Y208 and S211 from loop 7 of triosephosphate isomerase (TIM) form hydrogen bonds to backbone amides and carbonyls from loop 6 to stabilize the caged enzyme-substrate complex. The effect of seven mutations [Y208T, Y208S, Y208A, Y208F, S211G, S211A, Y208T/S211G] on the kinetic parameters for TIM catalyzed reactions of the whole substrates dihydroxyacetone phosphate and d-glyceraldehyde 3-phosphate [(k(cat)/K(m))(GAP) and (k(cat)/K(m))DHAP] and of the substrate pieces glycolaldehyde and phosphite dianion (k(cat)/K(HPi)K(GA)) are reported. The linear logarithmic correlation between these kinetic parameters, with slope of 1.04 ± 0.03, shows that most mutations of TIM result in an identical change in the activation barriers for the catalyzed reactions of whole substrate and substrate pieces, so that the transition states for these reactions are stabilized by similar interactions with the protein catalyst. The second linear logarithmic correlation [slope = 0.53 ± 0.16] between k(cat) for isomerization of GAP and K(d)(⧧) for phosphite dianion binding to the transition state for wildtype and many mutant TIM-catalyzed reactions of substrate pieces shows that ca. 50% of the wildtype TIM dianion binding energy, eliminated by these mutations, is expressed at the wildtype Michaelis complex, and ca. 50% is only expressed at the wildtype transition state. Negative deviations from this correlation are observed when the mutation results in a decrease in enzyme reactivity at the catalytic site. The main effect of Y208T, Y208S, and Y208A mutations is to cause a reduction in the total intrinsic dianion binding energy, but the effect of Y208F extends to the catalytic site.

Functionalized PHB granules provide the basis for the efficient side-chain cleavage of cholesterol and analogs in recombinant Bacillus megaterium.

PubMed

Gerber, Adrian; Kleser, Michael; Biedendieck, Rebekka; Bernhardt, Rita; Hannemann, Frank

2015-07-29

Cholesterol, the precursor of all steroid hormones, is the most abundant steroid in vertebrates and exhibits highly hydrophobic properties, rendering it a difficult substrate for aqueous microbial biotransformations. In the present study, we developed a Bacillus megaterium based whole-cell system that allows the side-chain cleavage of this sterol and investigated the underlying physiological basis of the biocatalysis. CYP11A1, the side-chain cleaving cytochrome P450, was recombinantly expressed in the Gram-positive soil bacterium B. megaterium combined with the required electron transfer proteins. By applying a mixture of 2-hydroxypropyl-β-cyclodextrin and Quillaja saponin as solubilizing agents, the zoosterols cholesterol and 7-dehydrocholesterol, as well as the phytosterol β-sitosterol could be efficiently converted to pregnenolone or 7-dehydropregnenolone. Fluorescence-microscopic analysis revealed that cholesterol accumulates in the carbon and energy storage-serving poly(3-hydroxybutyrate) (PHB) bodies and that the membrane proteins CYP11A1 and its redox partner adrenodoxin reductase (AdR) are likewise localized to their surrounding phospholipid/protein monolayer. The capacity to store cholesterol was absent in a mutant strain devoid of the PHB-producing polymerase subunit PhaC, resulting in a drastically decreased cholesterol conversion rate, while no effect on the expression of the recombinant proteins could be observed. We established a whole-cell system based on B. megaterium, which enables the conversion of the steroid hormone precursor cholesterol to pregnenolone in substantial quantities. We demonstrate that the microorganism's PHB granules, aggregates of bioplastic coated with a protein/phospholipid monolayer, are crucial for the high conversion rate by serving as substrate storage. This microbial system opens the way for an industrial conversion of the abundantly available cholesterol to any type of steroid hormones, which represent one of the

Precise low cost chain gears for heliostats

NASA Astrophysics Data System (ADS)

Liedke, Phillip; Lewandowski, Arkadiusz; Pfahl, Andreas; Hölle, Erwin

2016-05-01

This work investigates the potential of chain gears as precise and low cost driving systems for rim drive heliostats. After explaining chain gear basics the polygon effect and chain lengthening are investigated. The polygon effect could be measured by a heliostat with chain rim gear and the chain lengthening with an accordant test set up. Two gear stages are scope of this work: a rim gear and an intermediate gear. Dimensioning, pretensioning and designing for both stages are explained.

Site-specific protein backbone and side-chain NMR chemical shift and relaxation analysis of human vinexin SH3 domain using a genetically encoded {sup 15}N/{sup 19}F-labeled unnatural amino acid

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

Shi, Pan; School of Life Science, University of Science and Technology of China, Hefei, Anhui 230026; Xi, Zhaoyong

Research highlights: {yields} Chemical synthesis of {sup 15}N/{sup 19}F-trifluomethyl phenylalanine. {yields} Site-specific incorporation of {sup 15}N/{sup 19}F-trifluomethyl phenylalanine to SH3. {yields} Site-specific backbone and side chain chemical shift and relaxation analysis. {yields} Different internal motions at different sites of SH3 domain upon ligand binding. -- Abstract: SH3 is a ubiquitous domain mediating protein-protein interactions. Recent solution NMR structural studies have shown that a proline-rich peptide is capable of binding to the human vinexin SH3 domain. Here, an orthogonal amber tRNA/tRNA synthetase pair for {sup 15}N/{sup 19}F-trifluoromethyl-phenylalanine ({sup 15}N/{sup 19}F-tfmF) has been applied to achieve site-specific labeling of SH3 at threemore » different sites. One-dimensional solution NMR spectra of backbone amide ({sup 15}N){sup 1}H and side-chain {sup 19}F were obtained for SH3 with three different site-specific labels. Site-specific backbone amide ({sup 15}N){sup 1}H and side-chain {sup 19}F chemical shift and relaxation analysis of SH3 in the absence or presence of a peptide ligand demonstrated different internal motions upon ligand binding at the three different sites. This site-specific NMR analysis might be very useful for studying large-sized proteins or protein complexes.« less

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.

A new method of evaluating the side wall interference effect on airfoil angle of attack by suction from the side walls

NASA Technical Reports Server (NTRS)

Sawada, H.; Sakakibara, S.; Sato, M.; Kanda, H.; Karasawa, T.

1984-01-01

A quantitative evaluation method of the suction effect from a suction plate on side walls is explained. It is found from wind tunnel tests that the wall interference is basically described by the summation form of wall interferences in the case of two dimensional flow and the interference of side walls.

In vivo cough suppressive activity of pectic polysaccharide with arabinogalactan type II side chains of Piper nigrum fruits and its synergistic effect with piperine.

PubMed

Khawas, Sadhana; Nosáľová, Gabriela; Majee, Sujay Kumar; Ghosh, Kanika; Raja, Washim; Sivová, Veronika; Ray, Bimalendu

2017-06-01

Piper nigrum L. fruits are not only a prized spice, but also highly valued therapeutic agent that heals many ailments including asthma, cold and respiratory problems. Herein, we have investigated structural features and in vivo antitussive activity of three fractions isolated from Piper nigrum fruits. The water extract (PN-WE) upon fractionation with EtOH yielded two fractions: a soluble fraction (PN-eSf) and a precipitated (PN-ePf) one. The existence of a pectic polysaccharide with arabinogalactan type II side chains (147kDa) in PN-ePf and piperine in PN-eSf were revealed. Moreover, oligosaccharides providing fine structural details of side chains were generated from PN-ePf and then characterized. The parental water extract (PN-WE) that contained both pectic polysaccharide and piperine, after oral administration (50mgkg -1 body weight) to guinea pigs, showed antitussive activity comparable to codeine phosphate (10mgkg -1 body weight). The EtOH precipitated fraction (PN-ePf) containing pectic polysaccharide showed comparatively higher antitussive activity than EtOH soluble fraction (PN-eSf) that contained piperine, but their potencies are lower than the parental water extract. Significantly, the specific airway smooth muscle reactivity of all three fractions remained unchanged. Finally, pectic polysaccharide-piperine combination in parental extract synergistically enhances antitussive effect in guinea pigs. Copyright © 2017 Elsevier B.V. All rights reserved.

A Site Density Functional Theory for Water: Application to Solvation of Amino Acid Side Chains.

PubMed

Liu, Yu; Zhao, Shuangliang; Wu, Jianzhong

2013-04-09

We report a site density functional theory (SDFT) based on the conventional atomistic models of water and the universality ansatz of the bridge functional. The excess Helmholtz energy functional is formulated in terms of a quadratic expansion with respect to the local density deviation from that of a uniform system and a universal functional for all higher-order terms approximated by that of a reference hard-sphere system. With the atomistic pair direct correlation functions of the uniform system calculated from MD simulation and an analytical expression for the bridge functional from the modified fundamental measure theory, the SDFT can be used to predict the structure and thermodynamic properties of water under inhomogeneous conditions with a computational cost negligible in comparison to that of brute-force simulations. The numerical performance of the SDFT has been demonstrated with the predictions of the solvation free energies of 15 molecular analogs of amino acid side chains in water represented by SPC/E, SPC, and TIP3P models. For theTIP3P model, a comparison of the theoretical predictions with MD simulation and experimental data shows agreement within 0.64 and 1.09 kcal/mol on average, respectively.

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.

Client-Side Image Maps: Achieving Accessibility and Section 508 Compliance

ERIC Educational Resources Information Center

Beasley, William; Jarvis, Moana

2004-01-01

Image maps are a means of making a picture "clickable", so that different portions of the image can be hyperlinked to different URLS. There are two basic types of image maps: server-side and client-side. Besides requiring access to a CGI on the server, server-side image maps are undesirable from the standpoint of accessibility--creating…

Composition of the epicuticular waxes coating the adaxial side of Phyllostachys aurea leaves: Identification of very-long-chain primary amides.

PubMed

Racovita, Radu C; Jetter, Reinhard

2016-10-01

The present study presents comprehensive chemical analyses of cuticular wax mixtures of the bamboo Phyllostachys aurea. The epicuticular and intracuticular waxes were sampled selectively from the adaxial side of leaves on young and old plants and investigated by gas chromatography-mass spectrometry and flame ionization detection. The epi- and intracuticular layers on young and old leaves had wax loads ranging from 1.7 μg/cm(2) to 1.9 μg/cm(2). Typical very-long-chain aliphatic wax constituents were found with characteristic chain length patterns, including alkyl esters (primarily C48), alkanes (primarily C29), fatty acids (primarily C28 and C16), primary alcohols (primarily C28) and aldehydes (primarily C30). Alicyclic wax components were identified as tocopherols and triterpenoids, including substantial amounts of triterpenoid esters. Alkyl esters, alkanes, fatty acids and aldehydes were found in greater amounts in the epicuticular layer, while primary alcohols and most terpenoids accumulated more in the intracuticular wax. Alkyl esters occurred as mixtures of metamers, combining C20 alcohol with various acids into shorter ester homologs (C36C40), and a wide range of alcohols with C22 and C24 acids into longer esters (C42C52). Primary amides were identified, with a characteristic chain length profile peaking at C30. The amides were present exclusively in the epicuticular layer and thus at or near the surface, where they may affect plant-herbivore or plant-pathogen interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electrostatic Solvation Free Energy of Amino Acid Side Chain Analogs: Implications for the Validity of Electrostatic Linear Response in Water

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

Lin, Bin; Pettitt, Bernard M.

Electrostatic free energies of solvation for 15 neutral amino acid side chain analogs are computed. We compare three methods of varying computational complexity and accuracy for three force fields: free energy simulations, Poisson-Boltzmann (PB), and linear response approximation (LRA) using AMBER, CHARMM, and OPLSAA force fields. We find that deviations from simulation start at low charges for solutes. The approximate PB and LRA produce an overestimation of electrostatic solvation free energies for most of molecules studied here. These deviations are remarkably systematic. The variations among force fields are almost as large as the variations found among methods. Our study confirmsmore » that success of the approximate methods for electrostatic solvation free energies comes from their ability to evaluate free energy differences accurately.« less

Activity of 3-Ketosteroid 9α-Hydroxylase (KshAB) Indicates Cholesterol Side Chain and Ring Degradation Occur Simultaneously in Mycobacterium tuberculosis*

PubMed Central

Capyk, Jenna K.; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C.; Eltis, Lindsay D.

2011-01-01

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (kcat/Km) of KshAB for the CoA thioester substrates was 20–30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent KmO2 was 90 ± 10 μm in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ1 ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism. PMID:21987574

Activity of 3-ketosteroid 9α-hydroxylase (KshAB) indicates cholesterol side chain and ring degradation occur simultaneously in Mycobacterium tuberculosis.

PubMed

Capyk, Jenna K; Casabon, Israël; Gruninger, Robert; Strynadka, Natalie C; Eltis, Lindsay D

2011-11-25

Mycobacterium tuberculosis (Mtb), a significant global pathogen, contains a cholesterol catabolic pathway. Although the precise role of cholesterol catabolism in Mtb remains unclear, the Rieske monooxygenase in this pathway, 3-ketosteroid 9α-hydroxylase (KshAB), has been identified as a virulence factor. To investigate the physiological substrate of KshAB, a rhodococcal acyl-CoA synthetase was used to produce the coenzyme A thioesters of two cholesterol derivatives: 3-oxo-23,24-bisnorchol-4-en-22-oic acid (forming 4-BNC-CoA) and 3-oxo-23,24-bisnorchola-1,4-dien-22-oic acid (forming 1,4-BNC-CoA). The apparent specificity constant (k(cat)/K(m)) of KshAB for the CoA thioester substrates was 20-30 times that for the corresponding 17-keto compounds previously proposed as physiological substrates. The apparent K(m)(O(2)) was 90 ± 10 μM in the presence of 1,4-BNC-CoA, consistent with the value for two other cholesterol catabolic oxygenases. The Δ(1) ketosteroid dehydrogenase KstD acted with KshAB to cleave steroid ring B with a specific activity eight times greater for a CoA thioester than the corresponding ketone. Finally, modeling 1,4-BNC-CoA into the KshA crystal structure suggested that the CoA moiety binds in a pocket at the mouth of the active site channel and could contribute to substrate specificity. These results indicate that the physiological substrates of KshAB are CoA thioester intermediates of cholesterol side chain degradation and that side chain and ring degradation occur concurrently in Mtb. This finding has implications for steroid metabolites potentially released by the pathogen during infection and for the design of inhibitors for cholesterol-degrading enzymes. The methodologies and rhodococcal enzymes used to generate thioesters will facilitate the further study of cholesterol catabolism.

Two Distantly Spaced Basic Patches in the Flexible Domain of Huntingtin-Interacting Protein 1 (HIP1) Are Essential for the Binding of Clathrin Light Chain.

PubMed

Ybe, Joel A; Clegg, Mary E; Illingworth, Melissa; Gonzalez, Claire; Niu, Qian

2009-01-01

The interaction between HIP family proteins (HIP1 and HIP12/1R) and clathrin is fundamental to endocytosis. We used circular dichroism (CD) to study the stability of an HIP1 subfragment (aa468-530) that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83°C. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494). The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation in sla2p (S. cerevisiae), HIP1 from D. melanogaster, and HIP1 homolog ZK370.3 from C. elegans implies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms.

Two Distantly Spaced Basic Patches in the Flexible Domain of Huntingtin-Interacting Protein 1 (HIP1) Are Essential for the Binding of Clathrin Light Chain

PubMed Central

Ybe, Joel A.; Clegg, Mary E.; Illingworth, Melissa; Gonzalez, Claire; Niu, Qian

2009-01-01

The interaction between HIP family proteins (HIP1 and HIP12/1R) and clathrin is fundamental to endocytosis. We used circular dichroism (CD) to study the stability of an HIP1 subfragment (aa468-530) that is splayed open. CD thermal melts show HIP1 468-530 is only stable at low temperatures, but this HIP1 fragment contains a structural unit that does not melt out even at 83°C. We then created HIP1 mutants to probe our hypothesis that a short hydrophobic path in the opened region is the binding site for clathrin light chain. We found that the binding of hub/LCb was sensitive to mutating two distantly separated basic residues (K474 and K494). The basic patches marked by K474 and K494 are conserved in HIP12/1R. The lack of conservation in sla2p (S. cerevisiae), HIP1 from D. melanogaster, and HIP1 homolog ZK370.3 from C. elegans implies the binding of HIP1 and HIP1 homologs to clathrin light chain may be different in these organisms. PMID:22820750

Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network

PubMed Central

Zhu, Chongqin; Gao, Yurui; Li, Hui; Meng, Sheng; Li, Lei; Francisco, Joseph S.; Zeng, Xiao Cheng

2016-01-01

Hydrophobicity of macroscopic planar surface is conventionally characterized by the contact angle of water droplets. However, this engineering measurement cannot be directly extended to surfaces of proteins, due to the nanometer scale of amino acids and inherent nonplanar structures. To measure the hydrophobicity of side chains of proteins quantitatively, numerous parameters were developed to characterize behavior of hydrophobic solvation. However, consistency among these parameters is not always apparent. Herein, we demonstrate an alternative way of characterizing hydrophobicity of amino acid side chains in a protein environment by constructing a monolayer of amino acids (i.e., artificial planar peptide network) according to the primary and the β-sheet secondary structures of protein so that the conventional engineering measurement of the contact angle of a water droplet can be brought to bear. Using molecular dynamics simulations, contact angles θ of a water nanodroplet on the planar peptide network, together with excess chemical potentials of purely repulsive methane-sized Weeks−Chandler−Andersen solute, are computed. All of the 20 types of amino acids and the corresponding planar peptide networks are studied. Expectedly, all of the planar peptide networks with nonpolar amino acids are hydrophobic due to θ > 90°, whereas all of the planar peptide networks of the polar and charged amino acids are hydrophilic due to θ < 90°. Planar peptide networks of the charged amino acids exhibit complete-wetting behavior due to θ = 0°. This computational approach for characterization of hydrophobicity can be extended to artificial planar networks of other soft matter. PMID:27803319

Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network.

PubMed

Zhu, Chongqin; Gao, Yurui; Li, Hui; Meng, Sheng; Li, Lei; Francisco, Joseph S; Zeng, Xiao Cheng

2016-11-15

Hydrophobicity of macroscopic planar surface is conventionally characterized by the contact angle of water droplets. However, this engineering measurement cannot be directly extended to surfaces of proteins, due to the nanometer scale of amino acids and inherent nonplanar structures. To measure the hydrophobicity of side chains of proteins quantitatively, numerous parameters were developed to characterize behavior of hydrophobic solvation. However, consistency among these parameters is not always apparent. Herein, we demonstrate an alternative way of characterizing hydrophobicity of amino acid side chains in a protein environment by constructing a monolayer of amino acids (i.e., artificial planar peptide network) according to the primary and the β-sheet secondary structures of protein so that the conventional engineering measurement of the contact angle of a water droplet can be brought to bear. Using molecular dynamics simulations, contact angles θ of a water nanodroplet on the planar peptide network, together with excess chemical potentials of purely repulsive methane-sized Weeks-Chandler-Andersen solute, are computed. All of the 20 types of amino acids and the corresponding planar peptide networks are studied. Expectedly, all of the planar peptide networks with nonpolar amino acids are hydrophobic due to θ [Formula: see text] 90°, whereas all of the planar peptide networks of the polar and charged amino acids are hydrophilic due to θ [Formula: see text] 90°. Planar peptide networks of the charged amino acids exhibit complete-wetting behavior due to θ [Formula: see text] 0°. This computational approach for characterization of hydrophobicity can be extended to artificial planar networks of other soft matter.

Variation of the Side Chain Branch Position Leads to Vastly Improved Molecular Weight and OPV Performance in 4,8-dialkoxybenzo[1,2-b:4,5-b′]dithiophene/2,1,3-benzothiadiazole Copolymers

DOE PAGES

Coffin, Robert C.; MacNeill, Christopher M.; Peterson, Eric D.; ...

2011-01-01

Tmore » hrough manipulation of the solubilizing side chains, we were able to dramatically improve the molecular weight ( M w ) of 4,8-dialkoxybenzo[1,2- b :4,5- b ′ ]dithiophene (BD)/2,1,3-benzothiadiazole (B) copolymers. When dodecyl side chains ( P1 ) are employed at the 4- and 8-positions of the BD unit, we obtain a chloroform-soluble copolymer fraction with M w of 6.3 kg/mol. Surprisingly, by moving to the commonly employed 2-ethylhexyl branch ( P2 ), M w decreases to 3.4 kg/mol. his is despite numerous reports that this side chain increases solubility and M w . By moving the ethyl branch in one position relative to the polymer backbone (1-ethylhexyl, P3 ), M w is dramatically increased to 68.8 kg/mol. As a result of this M w increase, the shape of the absorption profile is dramatically altered, with λ max = 637 nm compared with 598 nm for P1 and 579 nm for P2 . he hole mobility as determined by thin film transistor (F) measurements is improved from ~ 1 × 10 − 6  cm 2 /Vs for P1 and P2 to 7 × 10 − 4  cm 2 /Vs for P3 , while solar cell power conversion efficiency in increased to 2.91 % for P3 relative to 0.31 % and 0.19 % for P1 and P2 , respectively.« less

Chlorination of Side Chains: A Strategy for Achieving a High Open Circuit Voltage Over 1.0 V in Benzo[1,2-b:4,5-b']dithiophene-Based Non-Fullerene Solar Cells

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

Chao, Pengjie; Mu, Zhao; Wang, Huan

Here, a benzo[1,2-b:4,5-b']dithiophene-based donor material with chlorine atoms substituted on its side chains, named PBClT, was designed and developed for application in non-fullerene solar cells to enhance the open-circuit voltage ( V oc) without decreasing charge carrier transfer in the corresponding blend films. The results demonstrated that the chlorinated PBClT polymer was an efficient donor in non-fullerene polymer solar cells (PSCs) and exhibited a blue-shifted absorbance, resulting in more complementary light absorption with non-fullerene acceptors, such as ITIC. In addition, the chlorine substitution decreased the HOMO level of PBClT, and as a result, the V oc of the corresponding solarmore » cell increased dramatically to 1.01 V, which is much higher than that of the non-chlorine analog, PTB7-Th, with a V oc of approximately 0.82 V. The 2D-GIWAX results illustrated that the PBClT/ITIC blend film exhibited a “face-on” orientation, which suggested that the chlorine substituents on the side chains favored π-π stacking in the direction perpendicular to the electron flow in photovoltaic devices. Furthermore, the PBClT/ITIC blend film showed a π-π stacking distance of 3.85 Å, which was very close to that of its non-chlorine analog blend film with a distance of approximately 3.74 Å. Based on this result, the introduction of multiple chlorine atoms on the conjugated side chains not only adjusted the energy level of the low-band-gap polymer through the electron withdrawing ability of the chlorine atoms but also subtly avoided obvious morphological changes that could result from strong steric hindrance in the main chain of the polymers. The PBClT/ITIC-based PSCs exhibited a maximum PCE of 8.46% with a V oc of 1.01 V, which is an increase in the PCE of approximately 22% compared to the PTB7-Th-based device based on our parallel experiments.« less

Chlorination of Side Chains: A Strategy for Achieving a High Open Circuit Voltage Over 1.0 V in Benzo[1,2-b:4,5-b']dithiophene-Based Non-Fullerene Solar Cells

DOE PAGES

Chao, Pengjie; Mu, Zhao; Wang, Huan; ...

2018-04-23

Here, a benzo[1,2-b:4,5-b']dithiophene-based donor material with chlorine atoms substituted on its side chains, named PBClT, was designed and developed for application in non-fullerene solar cells to enhance the open-circuit voltage ( V oc) without decreasing charge carrier transfer in the corresponding blend films. The results demonstrated that the chlorinated PBClT polymer was an efficient donor in non-fullerene polymer solar cells (PSCs) and exhibited a blue-shifted absorbance, resulting in more complementary light absorption with non-fullerene acceptors, such as ITIC. In addition, the chlorine substitution decreased the HOMO level of PBClT, and as a result, the V oc of the corresponding solarmore » cell increased dramatically to 1.01 V, which is much higher than that of the non-chlorine analog, PTB7-Th, with a V oc of approximately 0.82 V. The 2D-GIWAX results illustrated that the PBClT/ITIC blend film exhibited a “face-on” orientation, which suggested that the chlorine substituents on the side chains favored π-π stacking in the direction perpendicular to the electron flow in photovoltaic devices. Furthermore, the PBClT/ITIC blend film showed a π-π stacking distance of 3.85 Å, which was very close to that of its non-chlorine analog blend film with a distance of approximately 3.74 Å. Based on this result, the introduction of multiple chlorine atoms on the conjugated side chains not only adjusted the energy level of the low-band-gap polymer through the electron withdrawing ability of the chlorine atoms but also subtly avoided obvious morphological changes that could result from strong steric hindrance in the main chain of the polymers. The PBClT/ITIC-based PSCs exhibited a maximum PCE of 8.46% with a V oc of 1.01 V, which is an increase in the PCE of approximately 22% compared to the PTB7-Th-based device based on our parallel experiments.« less

GammaM23K, gammaM232K, and gammaL77K single substitutions in the TF1-ATPase lower ATPase activity by disrupting a cluster of hydrophobic side chains.

PubMed

Bandyopadhyay, Sanjay; Allison, William S

2004-07-27

In crystal structures of the bovine F(1)-ATPase (MF(1)), the side chains of gammaMet(23), gammaMet(232), and gammaLeu(77) interact in a cluster. Substitution of the corresponding residues in the alpha(3)beta(3)gamma subcomplex of TF(1) with lysine lowers the ATPase activity to 2.3, 11, and 15%, respectively, of that displayed by wild-type. In contrast, TF(1) subcomplexes containing the gammaM(23)C, gammaM(232)C, and gammaL(77)C substitutions display 36, 36, and 130%, respectively, of the wild-type ATPase activity. The ATPase activity of the gammaM(23)C/gammaM(232)C double mutant subcomplex is 36% that of the wild-type subcomplex before and after cross-linking the introduced cysteines, whereas the ATPase activity of the gammaM(23)C/L(77)C double mutant increased from 50 to 85% that of wild-type after cross-linking the introduced cysteines. Only beta-beta cross-links formed when the alpha(3)(betaE(395)C)(3)gammaM(23)C double mutant was inactivated with CuCl(2). The overall results suggest that the attenuated ATPase of the mutant subcomplexes containing the gammaM(23)K, gammaL(77)K, and gammaM(232)K substitutions is caused by disruption of the cluster of hydrophobic amino acid side chains and that the midregion of the coiled-coil comprised of the amino- and carboxyl-terminal alpha helices of the gamma subunit does not undergo unwinding or major displacement from the side chain of gammaLeu(77) during ATP-driven rotation of the gamma subunit.

A side-by-side comparison of CPV module and system performance

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

Muller, Matthew; Marion, Bill; Kurtz, Sarah

A side-by-side comparison is made between concentrator photovoltaic module and system direct current aperture efficiency data with a focus on quantifying system performance losses. The individual losses measured/calculated, when combined, are in good agreement with the total loss seen between the module and the system. Results indicate that for the given test period, the largest individual loss of 3.7% relative is due to the baseline performance difference between the individual module and the average for the 200 modules in the system. A basic empirical model is derived based on module spectral performance data and the tabulated losses between the modulemore » and the system. The model predicts instantaneous system direct current aperture efficiency with a root mean square error of 2.3% relative.« less

Fluorescence Determination of Tryptophan Side-Chain Accessibility and Dynamics in Triple-Helical Collagen-Like Peptides

PubMed Central

Simon-Lukasik, Kristine V.; Persikov, Anton V.; Brodsky, Barbara; Ramshaw, John A. M.; Laws, William R.; Alexander Ross, J. B.; Ludescher, Richard D.

2003-01-01

We report tryptophan fluorescence measurements of emission intensity, iodide quenching, and anisotropy that describe the environment and dynamics at X and Y sites in stable collagen-like peptides of sequence (Gly-X-Y)n. About 90% of tryptophans at both sites have similar solvent exposed fluorescence properties and a lifetime of 8.5–9 ns. Analysis of anisotropy decays using an associative model indicates that these long lifetime populations undergo rapid depolarizing motion with a 0.5 ns correlation time; however, the extent of fast motion at the Y site is considerably less than the essentially unrestricted motion at the X site. About 10% of tryptophans at both sites have a shorter (∼3 ns) lifetime indicating proximity to a protein quenching group; these minor populations are immobile on the peptide surface, depolarizing only by overall trimer rotation. Iodide quenching indicates that tryptophans at the X site are more accessible to solvent. Side chains at X sites are more solvent accessible and considerably more mobile than residues at Y sites and can more readily fluctuate among alternate intermolecular interactions in collagen fibrils. This fluorescence analysis of collagen-like peptides lays a foundation for studies on the structure, dynamics, and function of collagen and of triple-helical junctions in gelatin gels. PMID:12524302

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Enhanced n-Doping Efficiency of a Naphthalenediimide-Based Copolymer through Polar Side Chains for Organic Thermoelectrics

PubMed Central

2018-01-01

N-doping of conjugated polymers either requires a high dopant fraction or yields a low electrical conductivity because of their poor compatibility with molecular dopants. We explore n-doping of the polar naphthalenediimide–bithiophene copolymer p(gNDI-gT2) that carries oligoethylene glycol-based side chains and show that the polymer displays superior miscibility with the benzimidazole–dimethylbenzenamine-based n-dopant N-DMBI. The good compatibility of p(gNDI-gT2) and N-DMBI results in a relatively high doping efficiency of 13% for n-dopants, which leads to a high electrical conductivity of more than 10–1 S cm–1 for a dopant concentration of only 10 mol % when measured in an inert atmosphere. We find that the doped polymer is able to maintain its electrical conductivity for about 20 min when exposed to air and recovers rapidly when returned to a nitrogen atmosphere. Overall, solution coprocessing of p(gNDI-gT2) and N-DMBI results in a larger thermoelectric power factor of up to 0.4 μW K–2 m–1 compared to other NDI-based polymers. PMID:29457139

Enhanced n-Doping Efficiency of a Naphthalenediimide-Based Copolymer through Polar Side Chains for Organic Thermoelectrics.

PubMed

Kiefer, David; Giovannitti, Alexander; Sun, Hengda; Biskup, Till; Hofmann, Anna; Koopmans, Marten; Cendra, Camila; Weber, Stefan; Anton Koster, L Jan; Olsson, Eva; Rivnay, Jonathan; Fabiano, Simone; McCulloch, Iain; Müller, Christian

2018-02-09

N-doping of conjugated polymers either requires a high dopant fraction or yields a low electrical conductivity because of their poor compatibility with molecular dopants. We explore n-doping of the polar naphthalenediimide-bithiophene copolymer p(gNDI-gT2) that carries oligoethylene glycol-based side chains and show that the polymer displays superior miscibility with the benzimidazole-dimethylbenzenamine-based n-dopant N-DMBI. The good compatibility of p(gNDI-gT2) and N-DMBI results in a relatively high doping efficiency of 13% for n-dopants, which leads to a high electrical conductivity of more than 10 -1 S cm -1 for a dopant concentration of only 10 mol % when measured in an inert atmosphere. We find that the doped polymer is able to maintain its electrical conductivity for about 20 min when exposed to air and recovers rapidly when returned to a nitrogen atmosphere. Overall, solution coprocessing of p(gNDI-gT2) and N-DMBI results in a larger thermoelectric power factor of up to 0.4 μW K -2 m -1 compared to other NDI-based polymers.

Alanine scan of the peptide antibiotic feglymycin: assessment of amino acid side chains contributing to antimicrobial activity.

PubMed

Hänchen, Anne; Rausch, Saskia; Landmann, Benjamin; Toti, Luigi; Nusser, Antje; Süssmuth, Roderich D

2013-03-18

The antibiotic feglymycin is a linear 13-mer peptide synthesized by the bacterium Streptomyces sp. DSM 11171. It mainly consists of the nonproteinogenic amino acids 4-hydroxyphenylglycine and 3,5-dihydroxyphenylglycine. An alanine scan of feglymycin was performed by solution-phase peptide synthesis in order to assess the significance of individual amino acid side chains for biological activity. Hence, 13 peptides were synthesized from di- and tripeptide building blocks, and subsequently tested for antibacterial activity against Staphylococcus aureus strains. Furthermore we tested the inhibition of peptidoglycan biosynthesis enzymes MurA and MurC, which are inhibited by feglymycin. Whereas the antibacterial activity is significantly based on the three amino acids D-Hpg1, L-Hpg5, and L-Phe12, the inhibitory activity against MurA and MurC depends mainly on L-Asp13. The difference in the position dependence for antibacterial activity and enzyme inhibition suggests multiple molecular targets in the modes of action of feglymycin. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterisation of new types of side chain cholesteryl polymers.

PubMed

Wang, Bin; Du, Haiyan; Zhang, Junhua

2011-01-01

A series of cholesterol derivatives have been synthesised via the alkylation reaction of the 3-hydroxyl group with the aliphatic bromide compounds with different chain lengths, namely 3β-alkyloxy-cholesterol. The double bond between the C5 and C6 positions in these cholesterol derivatives was oxidised into epoxy, followed by an epoxy-ring-opening reaction with the treatment with acrylic acid, resulting in a series of 3β-alkyloxy-5α-hydroxy-6β-acryloyloxycholesterol, C(n)OCh (n=1, 2, 4, 6, 8, 10, 12), The acrylate group is connected to the C6 position, which is confirmed by the single crystal structure analysis. The corresponding polymers, PC(n)OCh, were prepared via free radical polymerisation. The structure of monomers and the resulting polymers were characterised with nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The thermal properties of PC(n)OCh were studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). To determine the secondary structure of polymers, circular dichroism (CD) spectra were performed. It was found that not all monomers produce high-molecular-weight polymers because of steric hindrance. However, all polymers have a helical structure, which can be enhanced by increasing the alkoxy chain length. In addition, increasing the alkoxy chain length decreases the glass transition temperature and increases the decomposition temperature of the polymers. Copyright © 2010 Elsevier Inc. All rights reserved.

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.

Project SIDE. Performance Report. 1992-1993.

ERIC Educational Resources Information Center

Alabama Southern Community Coll., Monroeville.

This document consists of the performance report and evaluation report of the second funding of Project SIDE, a workplace literacy project at Alabama Southern Community College (ASCC). The performance report contains the following: a list of the industrial partners; basic skills framework; chronological listing by company of courses offered;…

Effect of alkyl side chain location and cyclicity on the aerobic biotransformation of naphthenic acids.

PubMed

Misiti, Teresa M; Tezel, Ulas; Pavlostathis, Spyros G

2014-07-15

Aerobic biodegradation of naphthenic acids is of importance to the oil industry for the long-term management and environmental impact of process water and wastewater. The effect of structure, particularly the location of the alkyl side chain as well as cyclicity, on the aerobic biotransformation of 10 model naphthenic acids (NAs) was investigated. Using an aerobic, mixed culture, enriched with a commercial NA mixture (NA sodium salt; TCI Chemicals), batch biotransformation assays were conducted with individual model NAs, including eight 8-carbon isomers. It was shown that NAs with a quaternary carbon at the α- or β-position or a tertiary carbon at the β- and/or β'-position are recalcitrant or have limited biodegradability. In addition, branched NAs exhibited lag periods and lower degradation rates than nonbranched or simple cyclic NAs. Two NA isomers used in a closed bottle, aerobic biodegradation assay were mineralized, while 21 and 35% of the parent compound carbon was incorporated into the biomass. The NA biodegradation probability estimated by two widely used models (BIOWIN 2 and 6) and a recently developed model (OCHEM) was compared to the biodegradability of the 10 model NAs tested in this study as well as other related NAs. The biodegradation probability estimated by the OCHEM model agreed best with the experimental data and was best correlated with the measured NA biodegradation rate.

Continuous chain bit with downhole cycling capability

DOEpatents

Ritter, Don F.; St. Clair, Jack A.; Togami, Henry K.

1983-01-01

A continuous chain bit for hard rock drilling is capable of downhole cycling. A drill head assembly moves axially relative to a support body while the chain on the head assembly is held in position so that the bodily movement of the chain cycles the chain to present new composite links for drilling. A pair of spring fingers on opposite sides of the chain hold the chain against movement. The chain is held in tension by a spring-biased tensioning bar. A head at the working end of the chain supports the working links. The chain is centered by a reversing pawl and piston actuated by the pressure of the drilling mud. Detent pins lock the head assembly with respect to the support body and are also operated by the drilling mud pressure. A restricted nozzle with a divergent outlet sprays drilling mud into the cavity to remove debris. Indication of the centered position of the chain is provided by noting a low pressure reading indicating proper alignment of drilling mud slots on the links with the corresponding feed branches.

Looking east at the basic oxygen furnace building with gas ...

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

Looking east at the basic oxygen furnace building with gas cleaning plants in foreground on the left and the right side of the furnace building. - U.S. Steel Edgar Thomson Works, Basic Oxygen Steelmaking Plant, Along Monongahela River, Braddock, Allegheny County, PA

Preparation and Characterization of Polyurethanes with Cross-Linked Siloxane in the Side Chain by Sol-Gel Reactions

PubMed Central

Zhao, Hui; Hao, Tong-Hui; Hu, Guo-Hua; Shi, Dean; Huang, Da; Jiang, Tao; Zhang, Qun-Chao

2017-01-01

A series of novel polyurethanes containing cross-linked siloxane in the side chain (SPU) were successfully synthesized through a sol-gel process. The SPU was composed of 0%–20% N-(n-butyl)-3-aminopropyltriethoxysilane (HDI-T) modified hexamethylene diisocynate homopolymer. The effects of HDI-T content on both the structure and properties of SPU were investigated by Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), mechanical properties tests, gel content test, water contact angle measurement and water absorption test. FT-IR, XPS and XRD results confirmed the successful incorporation of HDI-T onto polyurethanes and the formation of Si–O–Si. The surface roughness and the Si content of SPU enhanced with the increase of HDI-T content. Both crystallization and melting temperature shifted to a lower point after the incorporation of HDI-T. The hydrophobicity, tensile strength, Young’s modulus and pencil hardness overall increased with the increasing of HDI-T content, whereas the thermal stability and the elongation at break of SPU slightly decreased. PMID:28772607

Amine-controlled assembly of metal-sulfite architecture from 1D chains to 3D framework.

PubMed

Austria, Cristina; Zhang, Jian; Valle, Henry; Zhang, Qichun; Chew, Emily; Nguyen, Dan-Tam; Gu, J Y; Feng, Pingyun; Bu, Xianhui

2007-08-06

Whereas open-framework materials have been made in a variety of chemical compositions, few are known in which 3-connected SO3(2)- anions serve as basic building units. Here, we report four new metal-sulfite polymeric structures, (ZnSO3)Py (1, py = pyridine), (ZnSO3)2(2,2'-bipy)H2O (2, 2,2'-bipy = 2,2'-bipyridine), (ZnSO3)2(TMDPy) (3, TMDPy = 4,4'-trimethylenedipyridine), and (MnSO3)2en (4, en = ethylenediamine) that have been synthesized hydrothermally and structurally characterized. In these compounds, low-dimensional 1D and 2D inorganic subunits are assembled into higher 2D or 3D covalent frameworks by organic ligands. In addition to the structure-directing effect of organic ligands, the flexible coordination chemistry of Zn2+ and SO3(2)- also contributes to the observed structural diversity. In compounds 1-3, Zn2+ sites alternate with trigonal pyramidal SO3(2)- anions to form three types of [ZnSO3]n chains, whereas in compound 4, a 2D-corrugated [MnSO3]n layer is present. Compound 1 features a rail-like chain with pendant pyridine rings. The pi-pi interaction between 2,2'-bipy ligands is found between adjacent chains in compound 2, resulting in 2D sheets that are further stacked through interlayer hydrogen bonds. Compound 3 exhibits a very interesting inorganic [(ZnSO3)2]n chain constructed from two chairlike subunits, and such chains are bridged by TMDPy ligands into a 2D sheet. In compound 4, side-by-side helical chains permeate through 2D-corrugated [MnSO3]n layers, which are pillared by neutral ethylenediamine molecules into a 3D framework that can be topologically represented as a (3,6)-connected net. The results presented here illustrate the rich structural chemistry of metal-sulfites and the potential of sulfite anions as a unique structural building block for the construction of novel open-framework materials, in particular, those containing polymeric inorganic subunits that may have interesting physical properties such as low-dimensional magnetism or

Restricted mobility of side chains on concave surfaces of solenoid proteins may impart heightened potential for intermolecular interactions.

PubMed

Ramya, L; Gautham, N; Chaloin, Laurent; Kajava, Andrey V

2015-09-01

Significant progress has been made in the determination of the protein structures with their number today passing over a hundred thousand structures. The next challenge is the understanding and prediction of protein-protein and protein-ligand interactions. In this work we address this problem by analyzing curved solenoid proteins. Many of these proteins are considered as "hub molecules" for their high potential to interact with many different molecules and to be a scaffold for multisubunit protein machineries. Our analysis of these structures through molecular dynamics simulations reveals that the mobility of the side-chains on the concave surfaces of the solenoids is lower than on the convex ones. This result provides an explanation to the observed preferential binding of the ligands, including small and flexible ligands, to the concave surface of the curved solenoid proteins. The relationship between the landscapes and dynamic properties of the protein surfaces can be further generalized to the other types of protein structures and eventually used in the computer algorithms, allowing prediction of protein-ligand interactions by analysis of protein surfaces. © 2015 Wiley Periodicals, Inc.

The Identification of Two Arabinosyltransferases from Tomato Reveals Functional Equivalency of Xyloglucan Side Chain Substituents1[W][OPEN

PubMed Central

Schultink, Alex; Cheng, Kun; Park, Yong Bum; Cosgrove, Daniel J.; Pauly, Markus

2013-01-01

Xyloglucan (XyG) is the dominant hemicellulose present in the primary cell walls of dicotyledonous plants. Unlike Arabidopsis (Arabidopsis thaliana) XyG, which contains galactosyl and fucosyl substituents, tomato (Solanum lycopersicum) XyG contains arabinofuranosyl residues. To investigate the biological function of these differing substituents, we used a functional complementation approach. Candidate glycosyltransferases were identified from tomato by using comparative genomics with known XyG galactosyltransferase genes from Arabidopsis. These candidate genes were expressed in an Arabidopsis mutant lacking XyG galactosylation, and two of them resulted in the production of arabinosylated XyG, a structure not previously found in this plant species. These genes may therefore encode XyG arabinofuranosyltransferases. Moreover, the addition of arabinofuranosyl residues to the XyG of this Arabidopsis mutant rescued a growth and cell wall biomechanics phenotype, demonstrating that the function of XyG in plant growth, development, and mechanics has considerable flexibility in terms of the specific residues in the side chains. These experiments also highlight the potential of reengineering the sugar substituents on plant wall polysaccharides without compromising growth or viability. PMID:23893172

Quasi-elastic neutron scattering study of a re-entrant side-chain liquid-crystal polyacrylate

NASA Astrophysics Data System (ADS)

Benguigui, L.; Noirez, L.; Kahn, R.; Keller, P.; Lambert, M.; Cohen de Lara, E.

1991-04-01

We present a first investigation of the dynamics of a side chain liquid crystal polyacrylate in the isotropic (I), nematic (N), smectic A (SA), and re-entrant nematic (NRe) phases by means of quasi-elastic neutron scattering. The motion or/and the mobility of the mesogen protons decreases as soon as the temperature decreases after the isotropic-nematic transition. The I-N and SA-NRe transitions corrspond to a jump in the curve of the Elastic Incoherent Structure Factor (ratio: elastic scattering/ total scattering) versus temperature, on the other hand the transition N-SA occurs without any change of slope. We conclude that the local order is very similar in the nematic and the smectic A phases. Nous présentons une première étude dynamique par diffusion quasi-élastique des neutrons, d'un échantillon de polyacrylate mésomorphe en peigne dans chacune des phases : isotrope, nématique, smectique et nématique rentrante. On montre que le mouvement et/ou la mobilité des protons du mésogène se restreint à mesure que la température diminue après la transition isotrope-nématique. Contrairement à la transition N-SA, les transitions I-N et SA-NRe correspondent à une discontinuité dans la courbe du Facteur de Structure Incohérent Elastique (rapport : intensité élastique/intensité totale) en fonction de la température ; l'ordre local semble donc très proche pour les phases nématique et smectique.

Disrupting Improvised Explosive Device Terror Campaigns: Basic Research Opportunities

DTIC Science & Technology

2008-01-01

2008 2. REPORT TYPE 3. DATES COVERED 00-00-2008 to 00-00-2008 4. TITLE AND SUBTITLE Disrupting Improvised Explosive Device Terror Campaigns... Explosive Device Terror Campaigns: Basic Research Opportunities A WORKSHOP REPORT Committee on Defeating Improvised Explosive Devices...iv v COMMITTEE ON DEFEATING IMPROVISED EXPLOSIVE DEVICES: BASIC RESEARCH TO INTERRUPT THE IED DELIVERY CHAIN Chairperson

Basic surface-active properties in the homologous series of β-alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides

PubMed Central

2013-01-01

Background Heterogeneous β-Alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides [R(EO)nPD] represent new “hybrid” nonionic-ionic colloidal structures in the field of surface-active products (technical products). These “niche” compounds have three structural and compositional characteristics that also define their basic colloidal properties: mixture of R and PEO chain homologues; specific conformations due to the PEO chains; and the presence of side products from the addition of higher alcohols, polyethyleneglycols and traces of water to acrylamide. The proposed major objective of this paper is the basic informative colloidal characterization (functional classification, HLB balance, surface tension, critical micelle concentration) in direct correlation with the structural changes in the homologous series of LM(EO)nPD and CS(EO)nPD. The structures were obtained either indirectly by cyanoethylation followed by partial acid hydrolysis of the corresponding β-propionitriles, or directly by the nucleophilic addition under alkaline catalysis of linear higher alcohols C12H25/C14H29 (7/3) (LM) and C16H33/C18H37 (CS) as such and heterogeneous polyethoxylated (n = 3-20) to acrylamide monomer, through an adapted classic reaction scheme. Results In the series of basic colloidal characteristics investigated the structure-surface activity dependence is confirmed. Their indicative character for R(EO)nPD is based on the assumption that the structures studied are not unitary (heterogeneous) because: a) the hydrophobic chains C12H25/C18H37 have been grouped in two variants, C12H25/C14H29 (LM); C16H33/C18H37 (CS), each with an internal mass ratio of 7/3; b) the hydrophilic polyoxyethylene chains (n = 3-20) have polydisperse character; the meaning and value the oligomerization degree, n, is that of weighted average. In these conditions the surface tension increases proportionally with the oligomerization degree of the polyoxyethylene chain, while the

Effect of the side chain spacer structure on the pH-responsive properties of polycarboxylates.

PubMed

Harada, Atsushi; Teranishi, Ryoma; Yuba, Eiji; Kono, Kenji

The properties of stimuli-responsive polymers change significantly with changes to their environment, such as temperature and pH. This behavior can be utilized for the preparation of stimuli-responsive carriers for efficient cytosolic delivery of active drugs. Among the possible environmental conditions, pH is one of the most useful stimuli because the pH in an endosome is lower than under physiological conditions, depending on endosomal development. This pH difference is an important factor in the design of pH-responsive polymers, which can be used to enhance the transport of endocytosed drugs from the endosomal compartment to the cytoplasm. Such polymers can destabilize the endosomal bilayer under mildly acidic conditions and be nondisruptive at pH 7.4 not only for efficient endosomal escape but also for the suppression of nonspecific interaction with lipids existing under physiological conditions. In this study, we developed polycarboxylates with well-controlled pH-responsive properties bearing various spacer structures with different hydrophobicity. 3-methyl glutarylated polyallylamine and 2-carboxy-cyclohexanoylated polyallylamine were synthesized through the reaction between primary amine of PAA and acid anhydrides. Side chain spacers with higher hydrophobicity induced significant interactions with liposomal membranes at higher pH. pH-destabilizing liposomes could be modulated through the changing the composition of spacer structures with different hydrophobicity. Such formulations may represent an attractive strategy for the improvement of cytosolic delivery of active molecules.

Evidence of a Structural Defect in Ice VII and the Side Chain Dependent Response of Small Model Peptides to Increased Pressure

PubMed Central

Scott, J. Nathan; Vanderkooi, Jane M.

2014-01-01

The effect of high pressure on the OH stretch of dilute HOD in D2O was examined using high pressure FTIR. It was found that at pressures directly above the ice VI to ice VII transition, ice VII displays a splitting in the OH absorption indicative of differing hydrogen bonding environments. This result is contrary to published structures of ice VII in which each OH oscillator should experience an identical electronic environment. The anomalous band was found to decrease in absorbance and finally disappear at ~43.0 kbar. In addition, the pressure response of the amide I′ and II′ bands of three small model peptides was examined. Analysis of these bands’ response to increased pressure indicates significant side chain dependence of their structural rearrangement, which may play a role in the composition of full length proteins of barophilic organisms. PMID:21740637

Coordinate tropic hormone regulation of mRNAs for insulin-like growth factor II and the cholesterol side-chain-cleavage enzyme, P450scc [corrected], in human steroidogenic tissues.

PubMed Central

Voutilainen, R; Miller, W L

1987-01-01

Insulin-like growth factors (IGFs) are single-chain polypeptides important for cell proliferation and growth. IGFs are produced in several tissues, suggesting that they function in a paracrine or autocrine fashion as well as functioning as endocrine hormones. We studied the hormonal regulation of IGF-I and IGF-II mRNA in human steroidogenic tissues. In cultured human ovarian granulosa cells, follicle-stimulating hormone, human chorionic gonadotropin, and dibutyryl cAMP increased IGF-II mRNA, but corticotropin [adrenocorticotropic hormone (ACTH)], chorionic somatomammotropin, growth hormone, prolactin, dexamethasone, estradiol, and progesterone had no effect. In cultured human fetal adrenal cells, ACTH and dibutyryl cAMP increased IGF-II mRNA accumulation, but human chorionic gonadotropin and angiotensin II did not. The same five size species of IGF-II mRNA were detected in transfer blots of RNA from granulosa cells and fetal adrenal cells, and all of these increased after hormonal stimuli. Dibutyryl cAMP also increased IGF-II mRNA accumulation in cultured human placental cells. Accumulation of mRNA for the cholesterol side-chain-cleavage monooxygenase [P450scc [corrected]; cholesterol, reduced-adrenal-ferredoxin:oxygen oxidoreductase (side-chain-cleaving), EC 1.14.15.6] was regulated in parallel with IGF-II mRNA in all these steroidogenic tissues. IGF-I mRNA was not detected in transfer blots of these RNAs, and the minimal amounts detected in dot blots showed no detectable change after any of the hormonal stimuli studied. The data indicate that the IGF-II gene is expressed in human steroidogenic tissues and is regulated by cAMP. These data suggest that IGF-II may act in an autocrine or paracrine fashion to stimulate the adrenal and gonadal growth stimulated by ACTH and gonadotropins, respectively. Images PMID:3031644

Accomplishment of Multifunctional π-Conjugated Polymers by Regulating the Degree of Side-Chain Fluorination for Efficient Dopant-Free Ambient-Stable Perovskite Solar Cells and Organic Solar Cells.

PubMed

Kranthiraja, Kakaraparthi; Park, Sang Ho; Kim, Hyunji; Gunasekar, Kumarasamy; Han, Gibok; Kim, Bumjoon J; Kim, Chang Su; Kim, Soohyun; Lee, Hyunjung; Nishikubo, Ryosuke; Saeki, Akinori; Jin, Sung-Ho; Song, Myungkwan

2017-10-18

We present an efficient approach to develop a series of multifunctional π-conjugated polymers (P1-P3) by controlling the degree of fluorination (0F, 2F, and 4F) on the side chain linked to the benzodithiophene unit of the π-conjugated polymer. The most promising changes were noticed in optical, electrochemical, and morphological properties upon varying the degree of fluorine atoms on the side chain. The properly aligned energy levels with respect to the perovskite and PCBM prompted us to use them in perovskite solar cells (PSCs) as hole-transporting materials (HTMs) and in bulk heterojunction organic solar cells (BHJ OSCs) as photoactive donors. Interestingly, P2 (2F) and P3 (4F) showed an enhanced power conversion efficiency (PCE) of 14.94%, 10.35% compared to P1 (0F) (9.80%) in dopant-free PSCs. Similarly, P2 (2F) and P3 (4F) also showed improved PCE of 7.93% and 7.43%, respectively, compared to P1 (0F) (PCE of 4.35%) in BHJ OSCs. The high photvoltaic performance of the P2 and P3 based photovotaic devices over P1 are well correlated with their energy level alignment, charge transporting, morphological and packing properties, and hole transfer yields. In addition, the P1-P3 based dopant-free PSCs and BHJ OSCs showed an excellent ambient stability up to 30 days without a significant drop in their initial performance.

Raman signature of the non-hydrogen-bonded tryptophan side chain in proteins: experimental and ab initio spectra of 3-methylindole in the gas phase

NASA Astrophysics Data System (ADS)

Combs, Amanda; McCann, Kathleen; Autrey, Daniel; Laane, Jaan; Overman, Stacy A.; Thomas, George J.

2005-02-01

3-Methylindole (3MI), which serves as a structural model for the tryptophan side chain in proteins, has been investigated using vapor phase Raman spectroscopy. The vapor phase spectrum of 3MI identifies the Raman signature of the indolyl moiety free of intermolecular interaction and extends previously reported solution Raman studies of 3MI and related tryptophan derivatives. The Raman spectrum of 3MI vapor is also complemented here with newly obtained vapor phase infrared data and ab initio calculations to refine and extend previous vibrational assignments. The present results provide an improved basis for assessing the dependence of the indolyl Raman signature on the local environment of the tryptophan side chain of proteins. The principal conclusions of this work are the following. (i) The vapor phase 3MI molecule exhibits Raman bands at 3506, 1585, 1409, 1349/1341 (Fermi doublet) and 881 cm-1, which differ greatly from their counterparts in the Raman spectrum of 3MI liquid and thus serve as spectral markers of the indolyl ring environment. (ii) The Fermi doublet relative intensity ratio (I1/I2, where I1 and I2 are, respectively, the Raman intensities of the higher and lower wavenumber components of the doublet) is highly sensitive to the state of 3MI condensation, consistent with the previously reported sensitivity of I1/I2 to solvent polarity. The maximum value of the intensity ratio (I1/I2=3.0) is observed for 3MI vapor, while the minimum value (I1/I2=0.43) is observed for 3MI in CHCl3 solution. Implications of the present results for Raman analysis of hydrogen bonding states, hydrophilic interactions and hydrophobic interactions of tryptophan residues in proteins are considered.

Energetics of side-chain partitioning of β-signal residues in unassisted folding of a transmembrane β-barrel protein

PubMed Central

Iyer, Bharat Ramasubramanian; Zadafiya, Punit; Vetal, Pallavi Vijay

2017-01-01

The free energy of water-to-interface amino acid partitioning is a major contributing factor in membrane protein folding and stability. The interface residues at the C terminus of transmembrane β-barrels form the β-signal motif required for assisted β-barrel assembly in vivo but are believed to be less important for β-barrel assembly in vitro. Here, we experimentally measured the thermodynamic contribution of all 20 amino acids at the β-signal motif to the unassisted folding of the model β-barrel protein PagP. We obtained the partitioning free energy for all 20 amino acids at the lipid-facing interface (ΔΔG0w,i(φ)) and the protein-facing interface (ΔΔG0w,i(π)) residues and found that hydrophobic amino acids are most favorably transferred to the lipid-facing interface, whereas charged and polar groups display the highest partitioning energy. Furthermore, the change in non-polar surface area correlated directly with the partitioning free energy for the lipid-facing residue and inversely with the protein-facing residue. We also demonstrate that the interface residues of the β-signal motif are vital for in vitro barrel assembly, because they exhibit a side chain–specific energetic contribution determined by the change in nonpolar accessible surface. We further establish that folding cooperativity and hydrophobic collapse are balanced at the membrane interface for optimal stability of the PagP β-barrel scaffold. We conclude that the PagP C-terminal β-signal motif influences the folding cooperativity and stability of the folded β-barrel and that the thermodynamic contributions of the lipid- and protein-facing residues in the transmembrane protein β-signal motif depend on the nature of the amino acid side chain. PMID:28592485

[Stimulation of DNA molecules association with amphiphilic derivatives of 1,3-diazaadamantane containing hydrophobic side chanins].

PubMed

Mamaeva, O K; Gabrielian, A G; Arutiunian, G L; Bocharova, T N; Smirnova, E A; Volodin, A A; Shchelkina, A K; Kaliuzhnyĭ, D N

2014-01-01

Earlier, a new class of compounds--amphiphilic derivatives of 1,3-diazaadamantanes, capable of facilitating the strand exchange in the system of short oligonucleotides was revealed. Longer hydrophobic side chains of 1,3-diazaadamantanes promoted stronger acceleration of the reaction. In this study, interaction with DNA of two 1,3-diazaadamantane derivatives containing different side chains was investigated by use of optical methods. Concentration of the investigated 1,3-diazaadamantans micelles formation were determined by the means of monitoring fluorescence intensity enhancement of 1-anilinonaphtalene-8-sulphonate probe; as well as the ranges of concentrations where the compounds/water mixtures existed as true solutions. 1,3-diazaadamantanes affinity to DNA was determined with Fluorescent Intercalator Displacement (FID) approach. Significant increase in hydrodynamic volume of short DNA hairpins in the complexes with 1,3-diazaadamantanes was revealed by estimation of the fluorescence polarization of ethidium bromide probe bound to the hairpins. Intermolecular association of DNA hairpins upon binding with 1,3-diazaadamantans was confirmed by Förster resonance energy transfer in system of an equimolar mixture of fluorescently labeled with Cy-3 and Cy-5 hairpins. In this study, the number of positive charges at 1,3-diazaadamantane derivatives containing side chains of different lengths was demonstrated to affect their affinity to DNA, whereas longer length of the hydrophobic side chains ensured more efficient interaction between the DNA duplexes that may facilitate, in particular, DNA strand exchange.

Side-chain conformation at the selectivity filter shapes the permeation free-energy landscape of an ion channel.

PubMed

Harpole, Tyler J; Grosman, Claudio

2014-08-05

On the basis of single-channel currents recorded from the muscle nicotinic acetylcholine receptor (AChR), we have recently hypothesized that the conformation adopted by the glutamate side chains at the first turn of the pore-lining α-helices is a key determinant of the rate of ion permeation. In this paper, we set out to test these ideas within a framework of atomic detail and stereochemical rigor by conducting all-atom molecular dynamics and Brownian dynamics simulations on an extensively validated model of the open-channel muscle AChR. Our simulations provided ample support to the notion that the different rotamers of these glutamates partition into two classes that differ markedly in their ability to catalyze ion conduction, and that the conformations of the four wild-type glutamates are such that two of them "fall" in each rotamer class. Moreover, the simulations allowed us to identify the mm (χ(1) ≅ -60°; χ(2) ≅ -60°) and tp (χ(1) ≅ 180°; χ(2) ≅ +60°) rotamers as the likely conduction-catalyzing conformations of the AChR's selectivity-filter glutamates. More generally, our work shows an example of how experimental benchmarks can guide molecular simulations into providing a type of structural and mechanistic insight that seems otherwise unattainable.

The Mendeleev Crater chain: A description and discussion of origin

NASA Technical Reports Server (NTRS)

Eppler, D.; Heiken, G.

1974-01-01

A 113-kilometer-long crater chain on the floor of Mendeleev Crater is the best morphological example of several similar chains on the lunar far side. Age relationships relative to Mendeleev Crater indicate that it is a younger feature that may have developed over a fault parallel to the lunar grid system. The dumbbell shape of the chain may be related to a differential stress along a fault crossing the floor that resulted in varying resistance to magma invasion.

[Psychoanalysis and Side Effect].

PubMed

Shirahase, Joichiro

2015-01-01

A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions.

PubMed

Henkel, Sebastian G; Ter Beek, Alexander; Steinsiek, Sonja; Stagge, Stefan; Bettenbrock, Katja; de Mattos, M Joost Teixeira; Sauter, Thomas; Sawodny, Oliver; Ederer, Michael

2014-01-01

For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear how they interplay in the regulation of ETC enzymes under micro-aerobic chemostat conditions. Also, there are diverse results which and how quinones (oxidised/reduced, ubiquinone/other quinones) are controlling the ArcBA two-component system. In the following a mathematical model of the E. coli ETC linked to basic modules for substrate uptake, fermentation product excretion and biomass formation is introduced. The kinetic modelling focusses on regulatory principles of the ETC for varying oxygen conditions in glucose-limited continuous cultures. The model is based on the balance of electron donation (glucose) and acceptance (oxygen or other acceptors). Also, it is able to account for different chemostat conditions due to changed substrate concentrations and dilution rates. The parameter identification process is divided into an estimation and a validation step based on previously published and new experimental data. The model shows that experimentally observed, qualitatively different behaviour of the ubiquinone redox state and the ArcA activity profile in the micro-aerobic range for different experimental conditions can emerge from a single network structure. The network structure features a strong feed-forward effect from the FNR regulatory system to the ArcBA regulatory system via a common control of the dehydrogenases of the ETC. The model supports the hypothesis that ubiquinone but not ubiquinol plays a key role in determining the activity of ArcBA in a glucose-limited chemostat at micro-aerobic conditions.

Lunar interferometric astronomy: Some basic questions

NASA Technical Reports Server (NTRS)

Woolf, Neville

1992-01-01

The author examines some basic questions as to why there should be astronomical facilities on the far side of the moon. The questions are ones of appropriateness, i.e., is this a proper use for human resources, what the real goals are, and are the present concepts the best match for the goals.

Scoring of Side-Chain Packings: An Analysis of Weight Factors and Molecular Dynamics Structures.

PubMed

Colbes, Jose; Aguila, Sergio A; Brizuela, Carlos A

2018-02-26

The protein side-chain packing problem (PSCPP) is a central task in computational protein design. The problem is usually modeled as a combinatorial optimization problem, which consists of searching for a set of rotamers, from a given rotamer library, that minimizes a scoring function (SF). The SF is a weighted sum of terms, that can be decomposed in physics-based and knowledge-based terms. Although there are many methods to obtain approximate solutions for this problem, all of them have similar performances and there has not been a significant improvement in recent years. Studies on protein structure prediction and protein design revealed the limitations of current SFs to achieve further improvements for these two problems. In the same line, a recent work reported a similar result for the PSCPP. In this work, we ask whether or not this negative result regarding further improvements in performance is due to (i) an incorrect weighting of the SFs terms or (ii) the constrained conformation resulting from the protein crystallization process. To analyze these questions, we (i) model the PSCPP as a bi-objective combinatorial optimization problem, optimizing, at the same time, the two most important terms of two SFs of state-of-the-art algorithms and (ii) performed a preprocessing relaxation of the crystal structure through molecular dynamics to simulate the protein in the solvent and evaluated the performance of these two state-of-the-art SFs under these conditions. Our results indicate that (i) no matter what combination of weight factors we use the current SFs will not lead to better performances and (ii) the evaluated SFs will not be able to improve performance on relaxed structures. Furthermore, the experiments revealed that the SFs and the methods are biased toward crystallized structures.

The Basic Economics of CD-ROM Pricing.

ERIC Educational Resources Information Center

Erkkila, John E.

1991-01-01

This explanation of how the basic economic model of pricing applies to the CD-ROM industry considers the supply and demand sides of the market and compares three distinct pricing strategies: (1) pricing to maximize profits; (2) average cost pricing; and (3) marginal cost pricing. (EAM)

Improved Modeling of Side-Chain–Base Interactions and Plasticity in Protein–DNA Interface Design

PubMed Central

Thyme, Summer B.; Baker, David; Bradley, Philip

2012-01-01

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed “motifs”) was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein–DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. PMID:22426128

Locations of Racism in Education: A Speech Act Analysis of a Policy Chain

ERIC Educational Resources Information Center

Arneback, Emma; Quennerstedt, Ann

2016-01-01

This article explores how racism is located in an educational policy chain and identifies how its interpretation changes throughout the chain. A basic assumption is that the policy formation process can be seen as a chain in which international, national and local policies are "links"--separate entities yet joined. With Sweden as the…

Systemic lupus erythematosus: molecular cloning and analysis of 22 individual recombinant monoclonal kappa light chains specifically hydrolyzing human myelin basic protein.

PubMed

Timofeeva, Anna M; Buneva, Valentina N; Nevinsky, Georgy A

2015-10-01

Antibodies hydrolyzing myelin basic protein (MBP) can play an important role in the pathogenesis of multiple sclerosis (MS) and systemic lupus erythematosus (SLE). An immunoglobulin light chain phagemid library derived from peripheral blood lymphocytes of patients with SLE was used. Small pools of phage particles displaying light chains with different affinities for MBP were isolated by affinity chromatography on MBP-Sepharose, and the fraction eluted with 0.5 M NaCl was used for preparation of individual monoclonal light chains (MLChs, 26-27 kDa). Seventy-two of 440 individual colonies were randomly chosen, expressed in Escherichia coli in a soluble form, and MLChs were purified by metal chelating chromatography. Twenty-two of 72 MLChs have high affinity and efficiently hydrolyze only MBP (not other control proteins) demonstrating various pH optima in a 5.7-9.0 range and different substrate specificity in the hydrolysis of four different MBP oligopeptides. Four MLChs demonstrated serine protease-like and three thiol protease-like activities, while 11 MLChs were metalloproteases. The activity of three MLChs was inhibited by both phenylmethylsulfonyl fluoride (PMSF) and Ethylenediaminetetraacetic acid (EDTA), two other by EDTA and iodoacetamide, and one by PMSF, EDTA, and iodoacetamide. The ratio of relative activity in the presence of Ca(2+), Mg(2+), Mn(2+), Ni(2+), Zn(2+), Cu(2+), and Co(2+) was individual for each of 22 MLCh preparations. It is the first examples of human MLChs, which probably can possess two or even three different proteolytic activities. These observations suggest an extreme diversity of anti-MBP abzymes in SLE patients. The immune systems of individual SLE patients can generate a variety of anti-MBP abzymes, which can attack MBP of myelin-proteolipid sheath of axons and play an important role in MS and SLE pathogenesis. Copyright © 2015 John Wiley & Sons, Ltd.

Side-chain dynamics of a detergent-solubilized membrane protein: Measurement of tryptophan and glutamine hydrogen-exchange rates in M13 coat protein by sup 1 H NMR spectroscopy

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

O'Neil, J.D.J.; Sykes, B.D.

M13 coat protein is a small (50 amino acids) lipid-soluble protein that becomes an integral membrane protein during the infection stage of the life cycle of the M13 phage and is therefore used as a model membrane protein. To study side-chain dynamics in the protein, the authors have measured individual hydrogen-exchange rates for a primary amide in the side chain of glutamine-15 and for the indole amine of tryptophan-26. The protein was solubilized with the use of perdeuteriated sodium dodecyl sulfate (SDS), and hydrogen-exchange rates were measured by using {sup 1}H nuclear magnetic resonance spectroscopy. The glutamine-15 syn proton exchangedmore » at a rate identical with that in glutamine model peptides except that the pH corresponding to minimum exchange was elevated by about 1.5 pH units. The tryptophan-26 indole amine proton exchange was biphasic, suggesting that two populations of tryptophan-26 exist. It is suggested that the two populations may reflect protein dimerization or aggregation in the SDS micelles. The pH values of minimum exchange for tryptophan-26 in both environments were also elevated by 1.3-1.9 pH units. This phenomenon is reproduced when small tryptophan- and glutamine-containing hydrophobic peptides are dissolved in the presence of SDS micelles. The electrostatic nature of this phenomenon is proven by showing that the minimum pH for exchange can be reduced by dissolving the hydrophobic peptides in the positively charged detergent micelle dodecyltrimethylammonium bromide.« less

Cysteine Racemization on IgG Heavy and Light Chains

PubMed Central

Zhang, Qingchun; Flynn, Gregory C.

2013-01-01

Under basic pH conditions, the heavy chain 220-light chain 214 (H220-L214) disulfide bond, found in the flexible hinge region of an IgG1, can convert to a thioether. Similar conditions also result in racemization of the H220 cysteine. Here, we report that racemization occurs on both H220 and L214 on an IgG1 with a λ light chain (IgG1λ) but almost entirely on H220 of an IgGl with a κ light chain (IgG1κ) under similar conditions. Likewise, racemization was detected at significant levels on H220 and L214 on endogenous human IgG1λ but only at the H220 position on IgG1κ. Low but measurable levels of d-cysteines were found on IgG2 cysteines in the hinge region, both with monoclonal antibodies incubated under basic pH conditions and on antibodies isolated from human serum. A simplified reaction mechanism involving reversible β-elimination on the cysteine is presented that accounts for both base-catalyzed racemization and thioether formation at the hinge disulfide. PMID:24142697

Reflecting on the Liberal Reflex: Rhetoric and the Politics of Acknowledgement in Basic Writing

ERIC Educational Resources Information Center

Pavesich, Matthew

2011-01-01

In the 1990s, leading rhetoric and composition scholars criticized basic writing programs for their "liberalism." Basic writing had its defenders, however, and the ensuing debate exposed deep rifts in the field. This article argues that neither side in this formative debate nor the more recent alternative models of teaching basic writing…

Internet-enabled collaborative agent-based supply chains

NASA Astrophysics Data System (ADS)

Shen, Weiming; Kremer, Rob; Norrie, Douglas H.

2000-12-01

This paper presents some results of our recent research work related to the development of a new Collaborative Agent System Architecture (CASA) and an Infrastructure for Collaborative Agent Systems (ICAS). Initially being proposed as a general architecture for Internet based collaborative agent systems (particularly complex industrial collaborative agent systems), the proposed architecture is very suitable for managing the Internet enabled complex supply chain for a large manufacturing enterprise. The general collaborative agent system architecture with the basic communication and cooperation services, domain independent components, prototypes and mechanisms are described. Benefits of implementing Internet enabled supply chains with the proposed infrastructure are discussed. A case study on Internet enabled supply chain management is presented.

Teaching Markov Chain Monte Carlo: Revealing the Basic Ideas behind the Algorithm

ERIC Educational Resources Information Center

Stewart, Wayne; Stewart, Sepideh

2014-01-01

For many scientists, researchers and students Markov chain Monte Carlo (MCMC) simulation is an important and necessary tool to perform Bayesian analyses. The simulation is often presented as a mathematical algorithm and then translated into an appropriate computer program. However, this can result in overlooking the fundamental and deeper…

Interplay of secondary structures and side-chain contacts in the denatured state of BBA1

NASA Astrophysics Data System (ADS)

Wen, Edward Z.; Luo, Ray

2004-08-01

The denatured state of a miniprotein BBA1 is studied under the native condition with the AMBER/Poisson-Boltzmann energy model and with the self-guided enhanced sampling technique. Forty independent trajectories are collected to sample the highly diversified denatured structures. Our simulation data show that the denatured BBA1 contains high percentage of native helix and native turn, but low percentage of native hairpin. Conditional population analysis indicates that the native helix formation and the native hairpin formation are not cooperative in the denatured state. Side-chain analysis shows that the native hydrophobic contacts are more preferred than the non-native hydrophobic contacts in the denatured BBA1. In contrast, the salt-bridge contacts are more or less nonspecific even if their populations are higher than those of hydrophobic contacts. Analysis of the trajectories shows that the native helix mostly initiates near the N terminus and propagates to the C terminus, and mostly forms from 310-helix/turn to α helix. The same analysis shows that the native turn is important but not necessary in its formation in the denatured BBA1. In addition, the formations of the two strands in the native hairpin are rather asymmetric, demonstrating the likely influence of the protein environment. Energetic analysis shows that the native helix formation is largely driven by electrostatic interactions in denatured BBA1. Further, the native helix formation is associated with the breakup of non-native salt-bridge contacts and the accumulation of native salt-bridge contacts. However, the native hydrophobic contacts only show a small increase upon the native helix formation while the non-native hydrophobic contacts stay essentially the same, different from the evolution of hydrophobic contacts observed in an isolated helix folding.

Functional modeling identifies paralogous solanesyl-diphosphate synthases that assemble the side chain of plastoquinone-9 in plastids.

PubMed

Block, Anna; Fristedt, Rikard; Rogers, Sara; Kumar, Jyothi; Barnes, Brian; Barnes, Joshua; Elowsky, Christian G; Wamboldt, Yashitola; Mackenzie, Sally A; Redding, Kevin; Merchant, Sabeeha S; Basset, Gilles J

2013-09-20

It is a little known fact that plastoquinone-9, a vital redox cofactor of photosynthesis, doubles as a precursor for the biosynthesis of a vitamin E analog called plastochromanol-8, the physiological significance of which has remained elusive. Gene network reconstruction, GFP fusion experiments, and targeted metabolite profiling of insertion mutants indicated that Arabidopsis possesses two paralogous solanesyl-diphosphate synthases, AtSPS1 (At1g78510) and AtSPS2 (At1g17050), that assemble the side chain of plastoquinone-9 in plastids. Similar paralogous pairs were detected throughout terrestrial plant lineages but were not distinguished in the literature and genomic databases from mitochondrial homologs involved in the biosynthesis of ubiquinone. The leaves of the atsps2 knock-out were devoid of plastochromanol-8 and displayed severe losses of both non-photoactive and photoactive plastoquinone-9, resulting in near complete photoinhibition at high light intensity. Such a photoinhibition was paralleled by significant damage to photosystem II but not to photosystem I. In contrast, in the atsps1 knock-out, a small loss of plastoquinone-9, restricted to the non-photoactive pool, was sufficient to eliminate half of the plastochromanol-8 content of the leaves. Taken together, these results demonstrate that plastochromanol-8 originates from a subfraction of the non-photoactive pool of plastoquinone-9. In contrast to other plastochromanol-8 biosynthetic mutants, neither the single atsps knock-outs nor the atsps1 atsps2 double knock-out displayed any defects in tocopherols accumulation or germination.

Finding Minimal Addition Chains with a Particle Swarm Optimization Algorithm

NASA Astrophysics Data System (ADS)

León-Javier, Alejandro; Cruz-Cortés, Nareli; Moreno-Armendáriz, Marco A.; Orantes-Jiménez, Sandra

The addition chains with minimal length are the basic block to the optimal computation of finite field exponentiations. It has very important applications in the areas of error-correcting codes and cryptography. However, obtaining the shortest addition chains for a given exponent is a NP-hard problem. In this work we propose the adaptation of a Particle Swarm Optimization algorithm to deal with this problem. Our proposal is tested on several exponents whose addition chains are considered hard to find. We obtained very promising results.

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

Basic Skills Resource Center. Part 2

DTIC Science & Technology

1985-05-01

side if neceseary and Identify by block number) Basic Skills Education Curriculum Development Learning Strategies Reading Comprehension Motivational ... Motivational Skills Training for Military Technical Training Students ...... Barbara L. McCombs 25 Problem 27 Purpose 27 Approach 28 - Phase 1 28 - Phase...and Learning ...... John J. Hedl , Jr. 53 Purpose of Project 55 Description of Work 55 V Products 56 Virtual Videodisc Software Requirements ...... J.D

The veto system of the DarkSide-50 experiment

DOE PAGES

Agnes, P.

2016-03-16

Here, nuclear recoil events produced by neutron scatters form one of the most important classes of background in WIMP direct detection experiments, as they may produce nuclear recoils that look exactly like WIMP interactions. In DarkSide-50, we both actively suppress and measure the rate of neutron-induced background events using our neutron veto, composed of a boron-loaded liquid scintillator detector within a water Cherenkov detector. This paper is devoted to the description of the neutron veto system of DarkSide-50, including the detector structure, the fundamentals of event reconstruction and data analysis, and basic performance parameters.

The veto system of the DarkSide-50 experiment

NASA Astrophysics Data System (ADS)

Agnes, P.; Agostino, L.; Albuquerque, I. F. M.; Alexander, T.; Alton, A. K.; Arisaka, K.; Back, H. O.; Baldin, B.; Biery, K.; Bonfini, G.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadonati, L.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cavalcante, P.; Chepurnov, A.; Cocco, A. G.; Covone, G.; Crippa, L.; D'Angelo, D.; D'Incecco, M.; Davini, S.; De Cecco, S.; De Deo, M.; De Vincenzi, M.; Derbin, A.; Devoto, A.; Di Eusanio, F.; Di Pietro, G.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Foster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giganti, C.; Goretti, A. M.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; Hackett, B. R.; Herner, K. R.; Hungerford, E. V.; Ianni, Aldo; Ianni, Andrea; James, I.; Johnson, T.; Jollet, C.; Keeter, K.; Kendziora, C. L.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Li, X.; Lissia, M.; Lombardi, P.; Luitz, S.; Ma, Y.; Machulin, I. N.; Mandarano, A.; Mari, S. M.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meyers, P. D.; Miletic, T.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B. J.; Muratova, V. N.; Musico, P.; Napolitano, J.; Nelson, A.; Odrowski, S.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Perasso, S.; Pocar, A.; Pordes, S.; Pugachev, D. A.; Qian, H.; Randle, K.; Ranucci, G.; Razeto, A.; Reinhold, B.; Renshaw, A. L.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Savarese, C.; Segreto, E.; Semenov, D. A.; Shields, E.; Singh, P. N.; Skorokhvatov, M. D.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; Unzhakov, E. V.; Vishneva, A.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A. W.; Westerdale, S.; Wilhelmi, J.; Wojcik, M. M.; Xiang, X.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.

2016-03-01

Nuclear recoil events produced by neutron scatters form one of the most important classes of background in WIMP direct detection experiments, as they may produce nuclear recoils that look exactly like WIMP interactions. In DarkSide-50, we both actively suppress and measure the rate of neutron-induced background events using our neutron veto, composed of a boron-loaded liquid scintillator detector within a water Cherenkov detector. This paper is devoted to the description of the neutron veto system of DarkSide-50, including the detector structure, the fundamentals of event reconstruction and data analysis, and basic performance parameters.

Roles of basic amino acid residues in the activity of μ-conotoxin GIIIA and GIIIB, peptide blockers of muscle sodium channels.

PubMed

Sato, Kazuki; Yamaguchi, Yoko; Ishida, Yukisato; Ohizumi, Yasushi

2015-04-01

To study in detail the roles of basic amino acid residues in the activity of μ-conotoxin GIIIA (μ-GIIIA) and GIIIB (μ-GIIIB), specific blockers of muscle sodium channels, seven analogs of μ-GIIIA, and two analogs of μ-GIIIB were synthesized. μ-GIIIA analogs were synthesized by replacing systematically the three Arg residues (Arg1, Arg13, and Arg19) with one, two, and three Lys residues. μ-GIIIB analogs were synthesized by replacing simultaneously all four Lys residues (Lys9, Lys11, Lys16, and Lys19) with Arg residues and further replacement of acidic Asp residues with neutral Ala residues. Circular dichroism spectra of the synthesized analogs suggested that the replacement did not affect the three dimensional structure. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the side chain guanidino group of Arg13 of μ-GIIIA was important for the activity, whereas that of Arg19 had little role for biological activity. Although [Arg9,11,16,19]μ-GIIIB showed higher activity than native μ-GIIIB, highly basic [Ala2,12, Arg9,11,16,19]μ-GIIIB showed lower activity, suggesting that there was an appropriate molecular basicity for the maximum activity. © 2014 John Wiley & Sons A/S.

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.

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 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.

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

Using spiral chain models for study of nanoscroll structures

NASA Astrophysics Data System (ADS)

Savin, Alexander V.; Sakovich, Ruslan A.; Mazo, Mikhail A.

2018-04-01

Molecular nanoribbons with different chemical structures can form scrolled packings possessing outstanding properties and application perspectives due to their morphology. Here, we propose a simplified two-dimensional model of the molecular chain that allows us to describe the molecular nanoribbon's scrolled packings of various structures as a spiral packaging chain. The model allows us to obtain the possible stationary states of single-layer nanoribbon scrolls of graphene, graphane, fluorographene, fluorographane (graphene hydrogenated on one side and fluorinated on the other side), graphone C4H (graphene partially hydrogenated on one side), and fluorographone C4F . The obtained states and the states of the scrolls found through all-atomic models coincide with good accuracy. We show the stability of scrolled packings and calculate the dependence of energy, the number of coils, and the inner and outer radius of the scrolled packing on the nanoribbon length. It is shown that a scrolled packing is the most energetically favorable conformation for nanoribbons of graphene, graphane, fluorographene, and fluorographane at large lengths. A double-scrolled packing when the nanoribbon is symmetrically rolled into a scroll from opposite ends is more advantageous for longer length nanoribbons of graphone and fluorographone. We show the possibility of the existence of scrolled packings for nanoribbons of fluorographene and the existence of two different types of scrolls for nanoribbons of fluorographane, which correspond to the left and right Archimedean spirals of the chain model. The simplicity of the proposed model allows us to consider the dynamics of molecular nanoribbon scrolls of sufficiently large lengths and at sufficiently large time intervals.

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.

Pancreatic neuroendocrine tumors: the basics, the gray zone, and the target.

PubMed

Kelgiorgi, Dionysia; Dervenis, Christos

2017-01-01

Pancreatic neuroendocrine tumors (PanNETs) manifest with a range of symptoms and pose a therapeutic challenge. A team approach, in which many specialists come together, is necessary in the quest for the best patient-tailored treatment. Disciplines such as oncology, surgery, basic science, endocrinology, radiology, and nuclear medicine need to work side by side, equally contributing to patient care and to advancing our better understanding of this fascinating disease.

Technical manual for basic version of the Markov chain nest productivity model (MCnest)

EPA Science Inventory

The Markov Chain Nest Productivity Model (or MCnest) integrates existing toxicity information from three standardized avian toxicity tests with information on species life history and the timing of pesticide applications relative to the timing of avian breeding seasons to quantit...

User’s manual for basic version of MCnest Markov chain nest productivity model

EPA Science Inventory

The Markov Chain Nest Productivity Model (or MCnest) integrates existing toxicity information from three standardized avian toxicity tests with information on species life history and the timing of pesticide applications relative to the timing of avian breeding seasons to quantit...

Cationic double-chained surfactant as pseudostationary phase in micellar electrokinetic capillary chromatography for drug separations.

PubMed

Li, Yanqing; Liu, Qian; Yao, Shouzhuo

2008-05-15

The cationic double-chained surfactant didodecyldimethylammonium bromide (DDAB) was used as pseudostationary phase (PSP) in micellar electrokinetic capillary chromatography (MEKC). Its performance on the three kinds of drugs, i.e., basic, acidic, and neutral drugs, was systematically investigated. Nicotine, cotinine, caffeine, lidocaine, and procaine were selected as the model basic drugs. Good baseline separation and high efficiency were obtained under the optimal separation condition that consisted of 50mM phosphate (pH 4.0) and 0.08 mM DDAB. Three basic phenylenediamine isomers can also be well separated with DDAB in buffer. In addition, DDAB can form cationic bilayer on the capillary wall, thus the wall adsorption of basic analytes was greatly suppressed. Compared with commonly used CTAB, the separation of basic drugs was significantly improved with a much lower amount of DDAB present in the buffer. The DDAB-involved MEKC also showed superiority to CTAB upon the separation of acidic drugs, amoxicillin and ampicillin. In the case of neutral compounds, a good separation of resorcinol, 1-naphthol and 2-naphthol was achieved with 0.1mM DDAB and 30% (v/v) acetonitrile (ACN) present in buffer. Hence, it was concluded that the double-chained cationic surfactant DDAB can be a good substitute for traditional single-chained surfactant CTAB in MEKC.

Glycosaminoglycan chain of dentin sialoprotein proteoglycan.

PubMed

Zhu, Q; Sun, Y; Prasad, M; Wang, X; Yamoah, A K; Li, Y; Feng, J; Qin, C

2010-08-01

Dentin sialophosphoprotein (DSPP) is processed into dentin sialoprotein (DSP) and dentin phosphoprotein. A molecular variant of rat DSP, referred to as "HMW-DSP", has been speculated to be a proteoglycan form of DSP. To determine if HMW-DSP is the proteoglycan form of DSP and to identify the glycosaminoglycan side-chain attachment site(s), we further characterized HMW-DSP. Chondroitinase ABC treatment reduced the migration rate for portions of rat HMW-DSP to the level of DSP. Disaccharide analysis showed that rat HMW-DSP contains glycosaminoglycan chains made of chondroitin-4-sulfate and has an average of 31-32 disaccharides/mol. These observations confirmed that HMW-DSP is the proteoglycan form of DSP (renamed "DSP-PG"). Edman degradation and mass spectrometric analyses of tryptic peptides from rat DSP-PG, along with substitution analyses of candidate Ser residues in mouse DSPP, confirmed that 2 glycosaminoglycan chains are attached to Ser(241) and Ser(253) in the rat, or Ser(242) and Ser(254) in the mouse DSPP sequence.

Structure-based design of ligands for protein basic domains: Application to the HIV-1 Tat protein

NASA Astrophysics Data System (ADS)

Filikov, Anton V.; James, Thomas L.

1998-05-01

peptidic and peptidomimetic linkers. The linkers were refined by varying the length and side chains of the linking residues, carrying out BPMC simulations, and evaluation of the binding free energy for the best energy conformation. The dissociation constant of the best ligand designed is estimated to be in the low- to mid-nanomolar range.

Homeotropic alignment of dendritic columnar liquid crystal induced by hydrogen-bonded triphenylene core bearing fluoroalkyl chains.

PubMed

Ishihara, Shinsuke; Furuki, Yusuke; Hill, Jonathan P; Ariga, Katsuhiko; Takeoka, Shinji

2014-07-01

A 1:3 molar complex of the fluoroalkyl side chain-substituted 2,6,10-tris-carboxymethoxy-3,7,11-tris(4,4,5,5,6,6,7,7,7-nonafluoroheptyloxy)triphenylene (TPF4) with the second generation dendron 3,5-bis(3,4-bis-dodecyloxybenzyloxy)-N-pyridin-4-yl-benzamide (DN) assembled through complementary hydrogen bonding to form a supramolecular columnar liquid crystal, which exhibited homeotropic alignment when sandwiched between octadecyltrichlorosilane (OTS)-coated or indium tin oxide (ITO)-coated glass plates due to specific interactions between the fluoroalkyl side chains and the substrates.

J Genes for Heavy Chain Immunoglobulins of Mouse

NASA Astrophysics Data System (ADS)

Newell, Nanette; Richards, Julia E.; Tucker, Philip W.; Blattner, Frederick R.

1980-09-01

A 15.8-kilobase pair fragment of BALB/c mouse liver DNA, cloned in the Charon 4Aλ phage vector system, was shown to contain the μ heavy chain constant region (CHμ ) gene for the mouse immunoglobulin M. In addition, this fragment of DNA contains at least two J genes, used to code for the carboxyl terminal portion of heavy chain variable regions. These genes are located in genomic DNA about eight kilobase pairs to the 5' side of the CHμ gene. The complete nucleotide sequence of a 1120-base pair stretch of DNA that includes the two J genes has been determined.

Functional Modeling Identifies Paralogous Solanesyl-diphosphate Synthases That Assemble the Side Chain of Plastoquinone-9 in Plastids*

PubMed Central

Block, Anna; Fristedt, Rikard; Rogers, Sara; Kumar, Jyothi; Barnes, Brian; Barnes, Joshua; Elowsky, Christian G.; Wamboldt, Yashitola; Mackenzie, Sally A.; Redding, Kevin; Merchant, Sabeeha S.; Basset, Gilles J.

2013-01-01

It is a little known fact that plastoquinone-9, a vital redox cofactor of photosynthesis, doubles as a precursor for the biosynthesis of a vitamin E analog called plastochromanol-8, the physiological significance of which has remained elusive. Gene network reconstruction, GFP fusion experiments, and targeted metabolite profiling of insertion mutants indicated that Arabidopsis possesses two paralogous solanesyl-diphosphate synthases, AtSPS1 (At1g78510) and AtSPS2 (At1g17050), that assemble the side chain of plastoquinone-9 in plastids. Similar paralogous pairs were detected throughout terrestrial plant lineages but were not distinguished in the literature and genomic databases from mitochondrial homologs involved in the biosynthesis of ubiquinone. The leaves of the atsps2 knock-out were devoid of plastochromanol-8 and displayed severe losses of both non-photoactive and photoactive plastoquinone-9, resulting in near complete photoinhibition at high light intensity. Such a photoinhibition was paralleled by significant damage to photosystem II but not to photosystem I. In contrast, in the atsps1 knock-out, a small loss of plastoquinone-9, restricted to the non-photoactive pool, was sufficient to eliminate half of the plastochromanol-8 content of the leaves. Taken together, these results demonstrate that plastochromanol-8 originates from a subfraction of the non-photoactive pool of plastoquinone-9. In contrast to other plastochromanol-8 biosynthetic mutants, neither the single atsps knock-outs nor the atsps1 atsps2 double knock-out displayed any defects in tocopherols accumulation or germination. PMID:23913686

Effects of hydrophobic helix length and side chain chemistry on biomimicry in peptoid analogues of SP-C.