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

PubMed

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

2014-12-08

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

78 FR 13379 - Xanthan Gum from Austria and China; Scheduling of the Final Phase of an Antidumping Investigation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

..., sugars, minerals, and salts. Xanthan gum is a polysaccharide produced by aerobic fermentation of... backbone of two P-1,4-D- Glucose monosaccharide units, the second with a trisaccharide side chain consisting of P-D-Mannose-(1,4)-P-DGlucuronic acid-(1,2)-a-D- Mannose monosaccharide units. The terminal...

78 FR 2251 - Xanthan Gum From Austria: Preliminary Determination of Sales at Less Than Fair Value and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-10

... limited to, sugars, minerals, and salts. Xanthan gum is a polysaccharide produced by aerobic fermentation... consists of a backbone of two P-1,4-D- Glucose monosaccharide units, the second with a trisaccharide side chain consisting of P-D-Mannose-(1,4)- P-DGlucuronic acid-(1,2) - a-D- Mannose monosaccharide units. The...

Structure-activity relationships of a-, ß1-, and d-Tomatines and Tomatidine Against Human Breast (MDA-MB-231), Gastric (KATO-III), and Prostate (PC3) Cancer Cells

USDA-ARS?s Scientific Manuscript database

Partial acid hydrolysis of the tetrasaccharide (lycotetraose) side chain of the tomato glycoalkaloid a-tomatine resulted in the formation of four products with three (ß1-tomatine), two ('-tomatine), one (d-tomatine), and zero (tomatidine) sugar residues. These compounds were isolated by chromatogra...

Sugar-binding sites on the surface of the carbohydrate-binding module of CBH I from Trichoderma reesei.

PubMed

Tavagnacco, Letizia; Mason, Philip E; Schnupf, Udo; Pitici, Felicia; Zhong, Linghao; Himmel, Michael E; Crowley, Michael; Cesàro, Attilio; Brady, John W

2011-05-01

Molecular dynamics simulations were carried out for a system consisting of the carbohydrate-binding module (CBM) of the cellulase CBH I from Trichoderma reesei (Hypocrea jecorina) in a concentrated solution of β-D-glucopyranose, to determine whether there is any tendency for the sugar molecules to bind to the CBM. In spite of the general tendency of glucose to behave as an osmolyte, a marked tendency for the sugar molecules to bind to the protein was observed. However, the glucose molecules tended to bind only to specific sites on the protein. As expected, the hydrophobic face of the sugar molecules, comprising the axial H1, H3, and H5 aliphatic protons, tended to adhere to the flat faces of the three tyrosine side chains on the planar binding surface of the CBM. However, a significant tendency to bind to a groove-like feature on the upper surface of the CBM was also observed. These results would not be inconsistent with a model of the mechanism for this globular domain in which the cellodextrin chain being removed from the surface of crystalline cellulose passes over the upper surface of the CBM, presumably then available for hydrolysis in the active site tunnel of this processive cellulase. Copyright © 2011 Elsevier Ltd. All rights reserved.

Visual Detection of Human Antibodies Using Sugar Chain-Immobilized Fluorescent Nanoparticles: Application as a Point of Care Diagnostic Tool for Guillain-Barré Syndrome.

PubMed

Shinchi, Hiroyuki; Yuki, Nobuhiro; Ishida, Hideharu; Hirata, Koichi; Wakao, Masahiro; Suda, Yasuo

2015-01-01

Sugar chain binding antibodies have gained substantial attention as biomarkers due to their crucial roles in various disorders. In this study, we developed simple and quick detection method of anti-sugar chain antibodies in sera using our previously developed sugar chain-immobilized fluorescent nanoparticles (SFNPs) for the point-of-care diagnostics. Sugar chain structure on SFNPs was modified with the sugar moieties of the GM1 ganglioside via our original linker molecule to detect anti-GM1 antibodies. The structures and densities of the sugar moieties immobilized on the nanoparticles were evaluated in detail using lectins and sera containing anti-GM1 antibodies from patients with Guillain-Barré syndrome, a neurological disorder, as an example of disease involving anti-sugar chain antibodies. When optimized SFNPs were added to sera from patients with Guillain-Barré syndrome, fluorescent aggregates were able to visually detect under UV light in three hours. The sensitivity of the detection method was equivalent to that of the current ELISA method used for the diagnosis of Guillain-Barré syndrome. These results suggest that our method using SFNPs is suitable for the point-of-care diagnostics of diseases involving anti-sugar chain antibodies.

Intact carbohydrate structures as part of the melanoidin skeleton.

PubMed

Cämmerer, Bettina; Jalyschko, Walentina; Kroh, Lothar W

2002-03-27

Model melanoidins from monomeric, oligomeric, and polymeric carbohydrates, and amino acids formed under aqueous as well as water-free reaction conditions, were submitted to acidic catalyzed hydrolysis. Their degradation products were detected qualitatively and quantitatively by HPTLC and HPLC-DAD. A considerable amount of monomer carbohydrates from hydrolysis of model melanoidins formed under water-free reaction conditions was detected. It can be seen clearly that the amount of carbohydrates released increased with increasing degree of polymerization of the carbohydrates used as starting material. In comparison, the hydrolysis of melanoidins formed in aqueous condition resulted in only a small glucose release. It seems that in the Maillard reaction under water-free conditions, a significant amount of di- and oligomer carbohydrates were incorporated into the melanoidin skeleton as complete oligomer with intact glycosidic bond, forming side chains at the melanoidin skeleton. Additional side chains could be formed by transglycosylation reactions. With increasing water content, hydrothermolytic as well as retro-aldol reactions of the starting carbonyl components became significant, and therefore the possibility of forming side chains decreased. The results are consistent with the postulated melanoidin structure being built up mainly from sugar degradation products, probably branched via amino compounds.

Development of sugar chain-binding single-chain variable fragment antibody to adult T-cell leukemia cells using glyco-nanotechnology and phage display method.

PubMed

Muchima, Kaname; Todaka, Taro; Shinchi, Hiroyuki; Sato, Ayaka; Tazoe, Arisa; Aramaki, Rikiya; Kakitsubata, Yuhei; Yokoyama, Risa; Arima, Naomichi; Baba, Masanori; Wakao, Masahiro; Ito, Yuji; Suda, Yasuo

2018-04-01

Adult T-cell leukemia (ATL) is an intractable blood cancer caused by the infection of human T-cell leukemia virus type-1, and effective medical treatment is required. It is known that the structure and expression levels of cell surface sugar chains vary depending on cell states such as inflammation and cancer. Thus, it is expected that the antibody specific for ATL cell surface sugar chain would be an effective diagnostic tool and a strong candidate for the development of an anti-ATL drug. Here, we developed a stable sugar chain-binding single-chain variable fragment antibody (scFv) that can bind to ATL cells using a fibre-type Sugar Chip and phage display method. The fiber-type Sugar Chips were prepared using O-glycans released from ATL cell lines. The scFv-displaying phages derived from human B cells (diversity: 1.04 × 108) were then screened using the fiber-type Sugar Chips, and an O-glycan-binding scFv was obtained. The flow cytometry analysis revealed that the scFv predominantly bound to ATL cell lines. The sugar chain-binding properties of the scFv was evaluated by array-type Sugar Chip immobilized with a library of synthetic glycosaminoglycan disaccharide structures. Highly sulphated disaccharide structures were found to have high affinity to scFv.

5-Ethynyl-2'-deoxycytidine: a DNA building block with a 'clickable' side chain.

PubMed

Seela, Frank; Mei, Hui; Xiong, Hai; Budow, Simone; Eickmeier, Henning; Reuter, Hans

2012-10-01

The title compound [systematic name: 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one], C(11)H(13)N(3)O(4), shows two conformations in the crystalline state. The N-glycosylic bonds of both conformers adopt similar conformations, with χ = -149.2 (1)° for conformer (I-1) and -151.4 (1)° for conformer (I-2), both in the anti range. The sugar residue of (I-1) shows a C2'-endo envelope conformation ((2)E, S-type), with P = 164.7 (1)° and τ(m) = 36.9 (1)°, while (I-2) shows a major C3'-exo sugar pucker (C3'-exo-C2'-endo, (3)T(2), S-type), with P = 189.2 (1)° and τ(m) = 33.3 (1)°. Both conformers participate in the formation of a layered three-dimensional crystal structure with a chain-like arrangement of the conformers. The ethynyl groups do not participate in hydrogen bonding, but are arranged in proximal positions.

Analysis of the intermediate size proteoglycans from the developing chick limb buds.

PubMed

Vasan, N

1982-08-01

Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical properties with development. This report describes proteoglycan intermediates (PG-I) that predominate in stage-34 limbs, and compares them with proteoglycan aggregates (PG-A) in stage-38 limbs. We analysed proteoglycans and their components extracted with guanidinium chloride by subjecting them to density gradient centrifugation, molecular sieve chromatography, electrophoretic separation, and selective enzymatic degradation. PG-I and PG-A have similar chondroitin sulphate composition, amino sugars, chondroitin sulphate side-chain length, glycoprotein link factors, and hyaluronic acid binding capacity, and both cross react with antisera prepared against cartilage-specific chick sternal proteoglycans. However, PG-I has lower molecular weight, lower buoyant density, and fewer chondroitin sulphate side chains on the protein core. The PG-I in the developing limb can be considered a mixture of smaller aggregates and cartilage-specific large monomers in which the former predominate.

Effects of sugars on lipid bilayers during dehydration--SAXS/WAXS measurements and quantitative model.

PubMed

Lenné, Thomas; Garvey, Christopher J; Koster, Karen L; Bryant, Gary

2009-02-26

We present an X-ray scattering study of the effects of dehydration on the bilayer and chain-chain repeat spacings of dipalmitoylphosphatidylcholine bilayers in the presence of sugars. The presence of sugars has no effect on the average spacing between the phospholipid chains in either the fluid or gel phase. Using this finding, we establish that for low sugar concentrations only a small amount of sugar exclusion occurs. Under these conditions, the effects of sugars on the membrane transition temperatures can be explained quantitatively by the reduction in hydration repulsion between bilayers due to the presence of the sugars. Specific bonding of sugars to lipid headgroups is not required to explain this effect.

Pyridylamination as a means of analyzing complex sugar chains

PubMed Central

Hase, Sumihiro

2010-01-01

Herein, I describe pyridylamination for versatile analysis of sugar chains. The reducing ends of the sugar chains are tagged with 2-aminopyridine and the resultant chemically stable fluorescent derivatives are used for structural/functional analysis. Pyridylamination is an effective “operating system” for increasing sensitivity and simplifying the analytical procedures including mass spectrometry and NMR. Excellent separation of isomers is achieved by reversed-phase HPLC. However, separation is further improved by two-dimensional HPLC, which involves a combination of reversed-phase HPLC and size-fractionation HPLC. Moreover, a two-dimensional HPLC map is also useful for structural analysis. I describe a simple procedure for preparing homogeneous pyridylamino sugar chains that is less laborious than existing techniques and can be used for functional analysis (e.g., sugar-protein interaction). This novel approach was applied and some of the results are described: i) a glucosyl-serine type sugar chain found in blood coagulation factors; ii) discovery of endo-β-mannosidase (EC 3.2.1.152) and a new type plant α1,2-l-fucosidase; and iii) novel substrate specificity of a cytosolic α-mannosidase. Moreover, using homogeneous sugar chains of a size similar to in vivo substrates we were able to analyze interactions between sugar chains and proteins such as enzymes and lectins in detail. Interestingly, our studies reveal that some enzymes recognize a wider region of the substrate than anticipated. PMID:20431262

Enzymatic Preparation of a Homologous Series of Long-Chain 6- O-Acylglucose Esters and Their Evaluation as Emulsifiers.

PubMed

Liang, Min-Yi; Chen, Yongsheng; Banwell, Martin G; Wang, Yong; Lan, Ping

2018-04-18

Sugar fatty acid esters are nonionic surfactants that are widely exploited in the food and cosmetics industries, as well as in the oral care and medical supply fields. Accordingly, new methods for their selective synthesis and the "tuning" of their emulsifying properties are of considerable interest. Herein we report simple and irreversible enzymatic esterifications of d-glucose with seven fatty acid vinyl esters. The foaming and emulsifying effects of the resulting 6- O-acylglucose esters were then evaluated. In accord with expectations, when the length of the alkyl side chain associated with the 6- O-acylglucose esters increases, then their hydrophilic-lipophilic balance (HLB) values decrease, while the stabilities of the derived emulsions improve. In order to maintain good foaming properties, alkyl side chains of at least 9 to 11 carbons in length are required. In the first such assays on 6- O-acylglucose esters, most of those described herein are shown to be nontoxic to the HepG2, MCF-7, LNacp, SW549, and LO-2 cell lines.

Added sugars in kids' meals from chain restaurants.

PubMed

Scourboutakos, Mary J; Semnani-Azad, Zhila; L'Abbé, Mary R

2016-06-01

To analyze the added sugars in kids' meals from Canadian chain restaurants in relation to the World Health Organization's proposed sugar recommendation (less than 5% of total daily calories should come from added sugars) and current recommendation (less than 10% of total daily calories should come from added sugars). Total sugar levels were retrieved from the websites of 10 fast-food and 7 sit-down restaurants in 2010. The added sugar levels in 3178 kids' meals from Canadian chain restaurants were calculated in 2014 (in Toronto, Canada) by subtracting all naturally occurring sugars from the total sugar level. The average amount of added sugars in restaurant kids' meals (25 ± 0.36 g) exceeded the WHO's proposed daily recommendation for sugar intake. There was a wide range of added sugar levels in kids' meals ranging from 0 g to 114 g. 50% of meals exceeded the WHO's proposed daily sugar recommendation, and 19% exceeded the WHO's current daily sugar recommendation. There is a wide range of sugar levels in kids' meals from restaurants, and many contain more than a day's worth of sugar.

Modification of Pectin and Hemicellulose Polysaccharides in Relation to Aril Breakdown of Harvested Longan Fruit

PubMed Central

Wang, Duoduo; Zhang, Haiyan; Wu, Fuwang; Li, Taotao; Liang, Yuxiang; Duan, Xuewu

2013-01-01

To investigate the modification of cell wall polysaccharides in relation to aril breakdown in harvested longan fruit, three pectin fractions (WSP, water soluble pectin; CSP, CDTA-soluble pectin; ASP, alkali soluble pectin) and one hemicellulose fraction (4 M KOH-SHC, 4 M KOH-soluble hemicellulose) were extracted, and their contents, monosaccharide compositions and molecular weights were evaluated. As aril breakdown intensified, CSP content increased while ASP and 4 M KOH-SHC contents decreased, suggesting the solubilization and conversion of cell wall components. Furthermore, the molar percentage of arabinose (Ara), as the main component of the side-chains, decreased largely in CSP and ASP while that of rhamnose (Rha), as branch point for the attachment of neutral sugar side chains, increased during aril breakdown. Analysis of (Ara + Gal)/Rha ratio showed that the depolymerization of CSP and ASP happened predominantly in side-chains formed of Ara residues. For 4 M KOH-SHC, more backbones were depolymerized during aril breakdown. Moreover, it was found that the molecular weights of CSP, ASP and 4 M KOH-SHC polysaccharides tended to decrease as aril breakdown intensified. These results suggest that both enhanced depolymerization and structural modifications of polysaccharides in the CSP, ASP and 4 M KOH-SHC fractions might be responsible for aril breakdown of harvested longan fruit. PMID:24287911

Neosordarin and hydroxysordarin, two new antifungal agents from Sordaria araneosa.

PubMed

Davoli, Paolo; Engel, Günther; Werle, Andreas; Sterner, Olov; Anke, Timm

2002-04-01

Two novel antifungal agents belonging to the sordarin family have been isolated from fermentations of Sordaria araneosa by bioassay-guided purification and their structures elucidated by NMR techniques. Neosordarin (1) is closely related to the recently discovered hypoxysordarin (2), with only small differences on the aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose moiety. Hydroxysordarin (3) closely resembles sordarin (4), the only slight difference being the replacement of sordarose with altrose as the sugar unit.

Chemical characterization of detrital sugar chains with peptides in oceanic surface particulate organic matter

NASA Astrophysics Data System (ADS)

Tsukasaki, A.; Nishida, T.; Tanoue, E.

2016-02-01

For better understanding of the dynamics of organic matter in the ocean interior, particulate organic matter (POM) in oceanic surface water is a key material as a starting material in food chain and biological carbon pump, and the source of dissolved organic matter. POM consists of a mixture of non-living POM (detritus) and small amount of living POM (organisms). Particulate combined amino acids (PCAAs) are one of the major components of POM and the most important source of nitrogen and carbon for heterotrophic organisms in marine environments. In our previous studies of molecular-level characterization of PCAAs using electrophoretic separation (SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis) with specific detection of protein/peptide and sugar chains, we reported that most of PCAAs existed as small-sized peptide chains with carbohydrate-rich remnants. Although carbohydrates are one of the major carbon components of POM, the details of molecular-level structures including sugar chains are unknown. In this study, we applied electrophoretic separation for sugar chains (FACE: fluorophore-assisted carbohydrate electrophoresis) to the POM samples collected from the surface water of the Pacific Ocean. The results showed that sugar chains with various degree of polymerization were detected in POM. The possible roles of such sugar chains in marine biogeochemical cycle of organic matter are discussed in the presentation.

Structural insight into mechanism and diverse substrate selection strategy of L-ribulokinase

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

Agarwal R.; Swaminathan S.; Burley, S. K.

2012-01-01

The araBAD operon encodes three different enzymes required for catabolism of L-arabinose, which is one of the most abundant monosaccharides in nature. L-ribulokinase, encoded by the araB gene, catalyzes conversion of L-ribulose to L-ribulose-5-phosphate, the second step in the catabolic pathway. Unlike other kinases, ribulokinase exhibits diversity in substrate selectivity and catalyzes phosphorylation of all four 2-ketopentose sugars with comparable k{sub cat} values. To understand ribulokinase recognition and phosphorylation of a diverse set of substrates, we have determined the X-ray structure of ribulokinase from Bacillus halodurans bound to L-ribulose and investigated its substrate and ATP co-factor binding properties. The polypeptidemore » chain is folded into two domains, one small and the other large, with a deep cleft in between. By analogy with related sugar kinases, we identified {sup 447}{und GG}LPQ{und K}{sup 452} as the ATP-binding motif within the smaller domain. L-ribulose binds in the cleft between the two domains via hydrogen bonds with the side chains of highly conserved Trp126, Lys208, Asp274, and Glu329 and the main chain nitrogen of Ala96. The interaction of L-ribulokinase with L-ribulose reveals versatile structural features that help explain recognition of various 2-ketopentose substrates and competitive inhibition by L-erythrulose. Comparison of our structure to that of the structures of other sugar kinases revealed conformational variations that suggest domain-domain closure movements are responsible for establishing the observed active site environment.« less

Structure of LacY with an α-substituted galactoside: Connecting the binding site to the protonation site

PubMed Central

Kumar, Hemant; Finer-Moore, Janet S.; Kaback, H. Ronald; Stroud, Robert M.

2015-01-01

The X-ray crystal structure of a conformationally constrained mutant of the Escherichia coli lactose permease (the LacY double-Trp mutant Gly-46→Trp/Gly-262→Trp) with bound p-nitrophenyl-α-d-galactopyranoside (α-NPG), a high-affinity lactose analog, is described. With the exception of Glu-126 (helix IV), side chains Trp-151 (helix V), Glu-269 (helix VIII), Arg-144 (helix V), His-322 (helix X), and Asn-272 (helix VIII) interact directly with the galactopyranosyl ring of α-NPG to provide specificity, as indicated by biochemical studies and shown directly by X-ray crystallography. In contrast, Phe-20, Met-23, and Phe-27 (helix I) are within van der Waals distance of the benzyl moiety of the analog and thereby increase binding affinity nonspecifically. Thus, the specificity of LacY for sugar is determined solely by side-chain interactions with the galactopyranosyl ring, whereas affinity is increased by nonspecific hydrophobic interactions with the anomeric substituent. PMID:26157133

Characterization of milled solid residue from cypress liquefaction in sub- and super ethanol.

PubMed

Liu, Hua-Min; Liu, Yu-Lan

2014-01-01

Cypress liquefaction in sub- and super ethanol was carried out in an autoclave at various temperatures. Milled solid residue (MSR) was isolated from solid residue remaining from the liquefaction process, and its chemical characteristics was comparatively investigated with milled wood lignin (MWL) of cypress by sugar analysis, elemental analysis, FT-IR analysis, gel permeation chromatography, and NMR analysis. Results showed that there were two reactions (de-polymerization and re-polymerization) during the cypress liquefaction in sub- and super ethanol and the re-polymerization reactions were the main reaction at 220-260°C. Considering the stability of side-chain, the stability of lignin side-chain in cypress during liquefaction process in ethanol could be sequenced as follows: β-5>β-β'>β-O-4'. The MSR were mainly from the decomposition and re-polymerization of lignin. This study suggests that characterization of MSR provides a promising method to investigate the mechanisms of cypress liquefaction in ethanol. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Mexico-U.S. Relations: Issues for Congress

DTIC Science & Technology

2008-12-18

States and Mexico recently resolved a long standing trade dispute involving sugar and high fructose corn syrup . Mexico argued that the sugar side...sugar side letter limited Mexican shipments of sugar. Mexico also complained that imports of high fructose corn syrup (HFCS) sweeteners from the...Mexican Congress imposed a 20% tax on soft drinks made with corn syrup sweeteners to aid the ailing domestic cane sugar industry, and subsequently

Mapping sugar beet pectin acetylation pattern.

PubMed

Ralet, Marie-Christine; Cabrera, Juan Carlos; Bonnin, Estelle; Quéméner, Bernard; Hellìn, Pilar; Thibault, Jean-François

2005-08-01

Homogalacturonan-derived partly methylated and/or acetylated oligogalacturonates were recovered after enzymatic hydrolysis (endo-polygalacturonase+pectin methyl esterase+side-chain degrading enzymes) of sugar beet pectin followed by anion-exchange and size exclusion chromatography. Around 90% of the GalA and 75% of the acetyl groups present in the initial sugar beet pectin were recovered as homogalacturonan-derived oligogalacturonates, the remaining GalA and acetyl belonging to rhamnogalacturonic regions. Around 50% of the acetyl groups present in sugar beet homogalacturonans were recovered as partly methylated and/or acetylated oligogalacturonates of degree of polymerisation 5 whose structures were determined by electrospray ionization ion trap mass spectrometry (ESI-IT-MSn). 2-O-acetyl- and 3-O-acetyl-GalA were detected in roughly similar amounts but 2,3-di-O-acetylation was absent. Methyl-esterified GalA residues occurred mainly upstream 2-O-acetyl GalA. Oligogalacturonates containing GalA residues that are at once methyl- and acetyl-esterified were recovered in very limited amounts. A tentative mapping of the distribution of acetyl and methyl esters within sugar beet homogalacturonans is proposed. Unsubstituted GalA residues are likely to be present in limited amounts (approximately 10% of total GalA residues), due to the fact that methyl and acetyl groups are assumed to be most often not carried by the same residues.

U.S.-Mexico Economic Relations: Trends, Issues, and Implications

DTIC Science & Technology

2012-01-25

States and Mexico resolved a long-standing trade dispute in 2006 involving sugar and high fructose corn syrup . Mexico argued that the sugar side letter...sugar side letter limited Mexican shipments of sugar. Mexico also complained that imports of high fructose corn syrup (HFCS) sweeteners from the United...Mexican Congress imposed a 20% tax on soft drinks made with corn syrup sweeteners to aid the ailing domestic cane sugar industry, and subsequently

Conformational dynamics of dry lamellar crystals of sugar based lipids: an atomistic simulation study.

PubMed

ManickamAchari, Vijayan; Bryce, Richard A; Hashim, Rauzah

2014-01-01

The rational design of a glycolipid application (e.g. drug delivery) with a tailored property depends on the detailed understanding of its structure and dynamics. Because of the complexity of sugar stereochemistry, we have undertaken a simulation study on the conformational dynamics of a set of synthetic glycosides with different sugar groups and chain design, namely dodecyl β-maltoside, dodecyl β-cellobioside, dodecyl β-isomaltoside and a C12C10 branched β-maltoside under anhydrous conditions. We examined the chain structure in detail, including the chain packing, gauche/trans conformations and chain tilting. In addition, we also investigated the rotational dynamics of the headgroup and alkyl chains. Monoalkylated glycosides possess a small amount of gauche conformers (∼20%) in the hydrophobic region of the lamellar crystal (LC) phase. In contrast, the branched chain glycolipid in the fluid Lα phase has a high gauche population of up to ∼40%. Rotational diffusion analysis reveals that the carbons closest to the headgroup have the highest correlation times. Furthermore, its value depends on sugar type, where the rotational dynamics of an isomaltose was found to be 11-15% and more restrained near the sugar, possibly due to the chain disorder and partial inter-digitation compared to the other monoalkylated lipids. Intriguingly, the present simulation demonstrates the chain from the branched glycolipid bilayer has the ability to enter into the hydrophilic region. This interesting feature of the anhydrous glycolipid bilayer simulation appears to arise from a combination of lipid crowding and the amphoteric nature of the sugar headgroups.

Weakly Hydrated Surfaces and the Binding Interactions of Small Biological Solutes

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

Brady, J. W.; Tavagnacco, L.; Ehrlich, L.

2012-04-01

Extended planar hydrophobic surfaces, such as are found in the side chains of the amino acids histidine, phenylalanine, tyrosine, and tryptophan, exhibit an affinity for the weakly hydrated faces of glucopyranose. In addition, molecular species such as these, including indole, caffeine, and imidazole, exhibit a weak tendency to pair together by hydrophobic stacking in aqueous solution. These interactions can be partially understood in terms of recent models for the hydration of extended hydrophobic faces and should provide insight into the architecture of sugar-binding sites in proteins.

Weakly hydrated surfaces and the binding interactions of small biological solutes.

PubMed

Brady, John W; Tavagnacco, Letizia; Ehrlich, Laurent; Chen, Mo; Schnupf, Udo; Himmel, Michael E; Saboungi, Marie-Louise; Cesàro, Attilio

2012-04-01

Extended planar hydrophobic surfaces, such as are found in the side chains of the amino acids histidine, phenylalanine, tyrosine, and tryptophan, exhibit an affinity for the weakly hydrated faces of glucopyranose. In addition, molecular species such as these, including indole, caffeine, and imidazole, exhibit a weak tendency to pair together by hydrophobic stacking in aqueous solution. These interactions can be partially understood in terms of recent models for the hydration of extended hydrophobic faces and should provide insight into the architecture of sugar-binding sites in proteins.

A Highly Sensitive Diagnostic System for Detecting Dengue Viruses Using the Interaction between a Sulfated Sugar Chain and a Virion.

PubMed

Saksono, Budi; Dewi, Beti Ernawati; Nainggolan, Leonardo; Suda, Yasuo

2015-01-01

We propose a novel method of detecting trace amounts of dengue virus (DENVs) from serum. Our method is based on the interaction between a sulfated sugar chain and a DENV surface glycoprotein. After capturing DENV with the sulfated sugar chain-immobilized gold nanoparticles (SGNPs), the resulting complex is precipitated and viral RNA content is measured using the reverse-transcription quantitative polymerase chain reaction SYBR Green I (RT-qPCR-Syb) method. Sugar chains that bind to DENVs were identified using the array-type sugar chain immobilized chip (Sugar Chip) and surface plasmon resonance (SPR) imaging. Heparin and low-molecular-weight dextran sulfate were identified as binding partners, and immobilized on gold nanoparticles to prepare 3 types of SGNPs. The capacity of these SGNPs to capture and concentrate trace amounts of DENVs was evaluated in vitro. The SGNP with greatest sensitivity was tested using clinical samples in Indonesia in 2013-2014. As a result, the novel method was able to detect low concentrations of DENVs using only 6 μL of serum, with similar sensitivity to that of a Qiagen RNA extraction kit using 140 μL of serum. In addition, this method allows for multiplex-like identification of serotypes of DENVs. This feature is important for good healthcare management of DENV infection in order to safely diagnose the dangerous, highly contagious disease quickly, with high sensitivity.

Effect of detergents on the H(+)-ATPase activity of inside-out and right-side-out plant plasma membrane vesicles.

PubMed

Palmgren, M G; Sommarin, M; Ulvskov, P; Larsson, C

1990-01-29

In search for a detergent to be used to assess the sidedness of plant plasma membrane vesicles by enzyme latency we tested the effect of 42 detergents on the ATPase activity of right-side-out and inside-out plasma membrane vesicles from sugar beet leaves. Most of the detergents seemed to inactivate the ATPase in addition to disrupting the permeability barrier to ATP. There were two main exceptions, namely long chain polyoxyethylene acyl ethers, such as detergents of the Brij series and Lubrol WX, and long chain lysophospholipids. These two types of detergents permeabilized the membranes at low concentrations and did not inhibit the ATPase at higher concentrations. Unmasking of latent active sites seemed to explain the activation of the plasma membrane H(+)-ATPase produced by long chain polyoxyethylene acyl ethers. These detergents should therefore be ideal for determination of vesicle orientation based on ATPase latency. By contrast, long chain lysophospholipids were found to be highly specific activators of the enzyme. In addition, long chain fatty acids were found to strongly inhibit ATP-dependent proton accumulation in the vesicles without inhibiting ATP hydrolysis. This uncoupling effect of the fatty acids could be abolished by the addition of fatty acid-free bovine serum albumin (BSA). Similarly, the proton transport capacity of ageing vesicles could be restored by addition of BSA. The latter findings may explain why isolated plasma membranes so often exhibit increased permeability to protons on ageing.

The biosynthesis of nitrogen-, sulfur-, and high-carbon chain-containing sugars.

PubMed

Lin, Chia-I; McCarty, Reid M; Liu, Hung-wen

2013-05-21

Carbohydrates serve many structural and functional roles in biology. While the majority of monosaccharides are characterized by the chemical composition (CH2O)n, modifications including deoxygenation, C-alkylation, amination, O- and N-methylation, which are characteristic of many sugar appendages of secondary metabolites, are not uncommon. Interestingly, some sugar molecules are formed via modifications including amine oxidation, sulfur incorporation, and "high-carbon" chain attachment. Most of these unusual sugars have been identified over the past several decades as components of microbially produced natural products, although a few high-carbon sugars are also found in the lipooligosaccharides of the outer cell walls of Gram-negative bacteria. Despite their broad distribution in nature, these sugars are considered "rare" due to their relative scarcity. The biosynthetic steps that underlie their formation continue to perplex researchers to this day and many questions regarding key transformations remain unanswered. This review will focus on our current understanding of the biosynthesis of unusual sugars bearing oxidized amine substituents, thio-functional groups, and high-carbon chains.

Chlorogenic acid-arabinose hybrid domains in coffee melanoidins: Evidences from a model system.

PubMed

Moreira, Ana S P; Coimbra, Manuel A; Nunes, Fernando M; Passos, Cláudia P; Santos, Sónia A O; Silvestre, Armando J D; Silva, André M N; Rangel, Maria; Domingues, M Rosário M

2015-10-15

Arabinose from arabinogalactan side chains was hypothesized as a possible binding site for chlorogenic acids in coffee melanoidins. To investigate this hypothesis, a mixture of 5-O-caffeoylquinic acid (5-CQA), the most abundant chlorogenic acid in green coffee beans, and (α1 → 5)-L-arabinotriose, structurally related to arabinogalactan side chains, was submitted to dry thermal treatments. The compounds formed during thermal processing were identified by electrospray ionization mass spectrometry (ESI-MS) and characterized by tandem MS (ESI-MS(n)). Compounds composed by one or two CQAs covalently linked with pentose (Pent) residues (1-12) were identified, along with compounds bearing a sugar moiety but composed exclusively by the quinic or caffeic acid moiety of CQAs. The presence of isomers was demonstrated by liquid chromatography online coupled to ESI-MS and ESI-MS(n). Pent1-2CQA were identified in coffee samples. These results give evidence for a diversity of chlorogenic acid-arabinose hybrids formed during roasting, opening new perspectives for their identification in melanoidin structures. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Sugar-binding and crystallographic studies of an arabinose-binding protein mutant (Met108Leu) that exhibits enhanced affinity and altered specificity.

PubMed

Vermersch, P S; Lemon, D D; Tesmer, J J; Quiocho, F A

1991-07-16

In addition to hydrogen bonds, van der Waals forces contribute to the affinity of protein-carbohydrate interactions. Nonpolar van der Waals contacts in the complexes of the L-arabinose-binding protein (ABP) with monosaccharides have been studied by means of site-directed mutagenesis, equilibrium and rapid kinetic binding techniques, and X-ray crystallography. ABP, a periplasmic transport receptor of Escherichia coli, binds L-arabinose, D-galactose, and D-fucose with preferential affinity in the order of Ara greater than Gal much greater than Fuc. Well-refined, high-resolution structures of ABP complexed with the three sugars revealed that the structural differences in the ABP-sugar complexes are localized around C5 of the sugars, where the equatorial H of Ara has been substituted for CH3 (Fuc) or CH2OH (Gal). The side chain of Met108 undergoes a sterically dictated, ligand-specific, conformational change to optimize nonpolar interactions between its methyl group and the sugar. We found that the Met108Leu ABP binds Gal tighter than wild-type ABP binds Ara and exhibits a preference for ligand in the order of Gal much greater than Fuc greater than Ara. The differences in affinity can be attributed to differences in the dissociation rates of the ABP-sugar complexes. We have refined at better than 1.7-A resolution the crystal structures of the Met108Leu ABP complexed with each of the sugars and offer a molecular explanation for the altered binding properties.

Simultaneous pretreatment and enzymatic hydrolysis of forage biomass

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

Henk, L.; Linden, J.C.

1993-12-31

Sweet sorghum is an attractive fermentation feedstock because as much as 40% of the dry weight consists of readily femented sugars such as sucrose, glucose and frutose. Cellulose and hemicellulose comprise another 50%. However, if this material is to be used a year-round feedstock for ethanol production, a stable method of storage must be developed to maintain the sugar content. A modified version of the traditional ensiling process is made effective by the addition of cellulolytic/hemicellulolytic enzymes and lactic acid bacteria to freshly chopped sweet sorghum prior to the production of silage. In situ hydrolysis of cellulose and hemicellulose occursmore » concurrently with the acidic ensiling fementation. By hydolyzing the acetyl groups using acetyl xylan esterase and 3-0-methyl glucuronyl side chains using pectinase from hemicellulose, cellulose becomes accessible to hydrolysis by cellulase, both during in situ ensiling with enzymes and in the simultaneous saccharification and fermentation (SSF) to ethanol.« less

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide-protein complexes.

PubMed

Kondo, Jiro; Westhof, Eric

2011-10-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide-protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson-Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson-Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues.

Classification of pseudo pairs between nucleotide bases and amino acids by analysis of nucleotide–protein complexes

PubMed Central

Kondo, Jiro; Westhof, Eric

2011-01-01

Nucleotide bases are recognized by amino acid residues in a variety of DNA/RNA binding and nucleotide binding proteins. In this study, a total of 446 crystal structures of nucleotide–protein complexes are analyzed manually and pseudo pairs together with single and bifurcated hydrogen bonds observed between bases and amino acids are classified and annotated. Only 5 of the 20 usual amino acid residues, Asn, Gln, Asp, Glu and Arg, are able to orient in a coplanar fashion in order to form pseudo pairs with nucleotide bases through two hydrogen bonds. The peptide backbone can also form pseudo pairs with nucleotide bases and presents a strong bias for binding to the adenine base. The Watson–Crick side of the nucleotide bases is the major interaction edge participating in such pseudo pairs. Pseudo pairs between the Watson–Crick edge of guanine and Asp are frequently observed. The Hoogsteen edge of the purine bases is a good discriminatory element in recognition of nucleotide bases by protein side chains through the pseudo pairing: the Hoogsteen edge of adenine is recognized by various amino acids while the Hoogsteen edge of guanine is only recognized by Arg. The sugar edge is rarely recognized by either the side-chain or peptide backbone of amino acid residues. PMID:21737431

Structural elucidation of rhamnogalacturonans from flaxseed hulls.

PubMed

Qian, Ke-Ying; Cui, Steve W; Nikiforuk, John; Goff, H Douglas

2012-11-15

The structure of acidic fraction gum (AFG) from flaxseed hulls was elucidated by methylation analysis and 1D/2D NMR spectroscopy. This acidic fraction was separated from water-soluble flaxseed gum using anion-exchange chromatography. AFG consisted of a rhamnogalacturonan-I (RG-I) backbone that features diglycosyl repeating units, →2)-α-l-Rhap-(1→4)-α-d-GalpA-(1→. Rhamnosyl residues (38.2%) were the most abundant neutral sugar component. It was present mainly as unbranched (16.5%) and branched (19.5%) →2)-α-l-Rhap-(1→ at O-3. Most of its branches were terminated by monosaccharides, α/β-d-Galp-(1→ (19.6%), α-l-Fucp-(1→ (4.5%) or β-d-Xylp-(1→ (3.1%). However, when this branching site was occasionally appended with →4)-α-d-GalpA-(1→ or →2)-α-l-Rhap-(1→, side chains may consist of rhamnogalacturonan-I (RG-I), homorhamnan (HR) or a mixture of both. AFG was highly branched as indicated by its high degree of branching (0.55). A possible structure of AFG was proposed: (HR, RG-I, and HG refer to homorhamnan, rhamnogalacturonan-I, and homogalacturonan, respectively. The locations of HR, RG-I, and HG are interchangeable; (m+n)/(n+i)≈1.5. The substitution rate of R(1) is ∼54%. R(1) is mostly monosaccharide (α/β-d-Galp-(1→, α-l-Fucp-(1→ or β-d-Xylp-(1→). R(1) may also occasionally be a longer side chain with more than two residues beginning with →4)-α-GalpA-(1→ or →2)-α-l-Rhap-(1→, wherein the side-chain structure may be similar to part of the main chain.). Copyright © 2012. Published by Elsevier Ltd.

High-sensitivity analysis of naturally occurring sugar chains, using a novel fluorescent linker molecule.

PubMed

Sato, Masaki; Ito, Yuji; Arima, Naomichi; Baba, Masanori; Sobel, Michael; Wakao, Masahiro; Suda, Yasuo

2009-07-01

To analyse the binding of sugar chains to proteins, viruses and cells, the surface plasmon resonance (SPR) technique is very convenient and effective because it is a real-time, non-destructive detection system. Key to this method is linker compounds for immobilization of the sugar chains to the gold-coated chip for SPR. Also, well-designed fluorescent labelling reagents are essential when analysing the structure of trace amounts of sugar chains derived from natural sources, such as glycoproteins on the surface of specific cells. In this report, we developed a novel linker molecule, named 'f-mono', which has both of these properties: simple immobilization chemistry and a fluorescent label. Since the molecule contains a 2,5-diaminopyridyl group and a thioctic acid group, conjugation with sugar chains can be achieved using the well-established reductive amination reaction. This conjugate of sugar chain and fluorescent linker (fluorescent ligand-conjugate, FLC) has fluorescent properties (ex. 335 nm, em. 380 nm), and as little as 1 microg of FLC can be easily purified using HPLC with a fluorescent detector. MS and MS/MS analysis of the FLC is also possible. As a +2 Da larger MS peak ([M + H + 2](+) ion) was always associated with the theoretical MS peak ([M + H](+)) (due to the reduction of the thioctic acid moiety), the MS peaks of the FLC were easily found, even using unfractionated crude samples. Immobilization of the FLC onto gold-coated chips, and their subsequent SPR analyses were successively accomplished, as had been performed previously using non-fluorescent ligand conjugates.

Semiquantitative determination of short-chain fatty acids in cane and beet sugars.

PubMed

Batista, Rebecca B; Grimm, Casey C; Godshall, Mary An

2002-03-01

Some sugars, specifically white beet sugar and raw cane sugars, possess off-flavors and off-odors. Although not necessarily the source, the presence of short-chain fatty acids serves as an indicator of an off-odor problem in sugar. Solid-phase microextraction (SPME) is used to collect the volatile compounds from the headspace of sugar. The temperature, moisture, and type of SPME fiber are varied to optimize recovery. Sugars analyzed in the absence of water using an incubation temperature of 70 degrees C with a divinylbenzene-carboxen-polydimethylsiloxane fiber yield the most reproducible results. Data from depletion analyses report a recovery level of 38% for the first injection. The semiquantitative analysis of butyric acid is accomplished using injected standards to develop a calibration curve.

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

PubMed Central

Takeuchi, M; Inoue, N; Strickland, T W; Kubota, M; Wada, M; Shimizu, R; Hoshi, S; Kozutsumi, H; Takasaki, S; Kobata, A

1989-01-01

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. PMID:2813359

Evidence for an intermediate conformational state of LacY.

PubMed

Jiang, Xiaoxu; Guan, Lan; Zhou, Yonggang; Hong, Wen-Xu; Zhang, Qinghai; Kaback, H Ronald

2012-03-20

LacY mutant Cys154 → Gly exhibits a periplasmic-closed crystal structure identical to the WT, but is periplasmic-open in the membrane. The mutant hardly catalyzes transport, but binds galactosides from either side of the membrane with the same affinity and is resistant to site-directed proteolysis relative to the pseudo-WT. Site-directed alkylation was also applied to 11 single-Cys mutants in Cys154 → Gly LacY in right-side-out membrane vesicles or after solubilization and purification in dodecyl-β-D-maltopyranoside (DDM). Unlike the pseudo-WT, Cys replacements on the periplasmic side of the Cys154 → Gly mutant label rapidly in the membrane without sugar, but labeling decreases markedly after the mutant proteins are purified. Thus, Cys154 → Gly LacY likely favors a higher-energy intermediate periplasmic-open conformation in situ, but collapses to a lower-energy periplasmic-closed conformation in DDM after purification. Notably, branched-chain or neopentyl glycol maltoside detergents stabilize Cys154 → Gly LacY in the membrane-embedded form.

Strong liquid-crystalline polymeric compositions

DOEpatents

Dowell, Flonnie

1993-01-01

Strong liquid-crystalline polymeric (LCP) compositions of matter. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment.

Absence of arabinan in the side chains of the pectic polysaccharides strongly associated with cell walls of Nicotiana plumbaginifolia non-organogenic callus with loosely attached constituent cells.

PubMed

Iwai, H; Ishii, T; Satoh, S

2001-10-01

When leaf disks from haploid plants of Nicotiana plumbaginifolia Viv. were transformed with T-DNA and cultured on shoot-inducing medium, nonorganogenic callus. designated nolac (for non-organogenic callus with loosely attached cells), appeared on approximately 7% of leaf disks. In contrast, normal callus was generated on T-DNA-transformed leaf disks from diploid plants and on non-transformed leaf disks from haploid and diploid plants. Transmission electron microscopy revealed that the middle lamellae and the cell walls of one line of mutant callus (nolac-H14) were barely stained by ruthenium red. even after demethylesterification with NaOH, whereas the entire cell wall and the middle lamella were strongly stained in normal callus. In cultures of nolac-H14 callus, the level of sugar components of pectic polysaccharides in the hemicellulose fraction was reduced and that in the culture medium was elevated, as compared with cultures of normal callus. These results indicate that pectic polysaccharides are not retained in the cell walls and middle lamellae of nolac-H14 callus. In nolac-H14, the ratio of arabinose to galactose was low in the pectic polysaccharides purified from all cell wall fractions and from the medium, in particular, in the hemicellulose fractions. The low levels of arabinofuranosyl (T-Araf, 5-Araf, 2,5-Araf, and 3,5-Araf) residues in the pectic polysaccharides of the hemicellulosic fraction of nolac-H,14 indicated that no neutral-sugar side chains, composed mainly of linear arabinan. were present in nolac-H14. Arabinose-rich pectins. which are strongly associated with cellulose-hemicellulose complexes, might play an important role in intercellular attachment in the architecture of the cell wall.

The Biosynthesis of Nitrogen-, Sulfur-, and High-carbon Chain-containing Sugars†

PubMed Central

Lin, Chia-I; McCarty, Reid M.; Liu, Hung-wen

2013-01-01

Carbohydrates serve many structural and functional roles in biology. While the majority of monosaccharides are characterized by the chemical composition: (CH2O)n, modifications including deoxygenation, C-alkylation, amination, O- and N-methylation, which are characteristic of many sugar appendages of secondary metabolites, are not uncommon. Interestingly, some sugar molecules are formed via modifications including amine oxidation, sulfur incorporation, and “high-carbon” chain attachment. Most of these unusual sugars have been identified over the past several decades as components of microbially produced natural products, although a few high-carbon sugars are also found in the lipooligosaccharides of the outer cell walls of Gram-negative bacteria. Despite their broad distribution in nature, these sugars are considered “rare” due to their relative scarcity. The biosynthetic steps that underlie their formation continue to perplex researchers to this day and many questions regarding key transformations remain unanswered. This review will focus on our current understanding of the biosynthesis of unusual sugars bearing oxidized amine substituents, thio-functional groups, and high-carbon chains. PMID:23348524

Strong liquid-crystalline polymeric compositions

DOEpatents

Dowell, F.

1993-12-07

Strong liquid-crystalline polymeric (LCP) compositions of matter are described. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment. 27 figures.

Side Effects of Immunosuppressant Medications as They Affect Physical Fitness: A Physical Therapist's Point of View

MedlinePlus

... Another side effect of immunosuppressant medications is hyperglycemia (high blood sugar) and secondary diabetes because they may alter the way your body manages glucose (sugar). It is important to routinely check your ...

[Sugar Chain Construction of Functional Natural Products Using Plant Glucosyltransferases].

PubMed

Mizukami, Hajime

2015-01-01

Plant secondary product glycosyltransferases belong to family 1 of the glycosyltransferase superfamily and mediate the transfer of a glycosyl residue from activated nucleotide sugars to lipophilic small molecules, thus affecting the solubility, stability and pharmacological activities of the sugar-accepting compounds. The biotechnological application of plant glycosyltransferases in glycoside synthesis has attracted attention because enzymatic glycosylation offers several advantages over chemical methods, including (1) avoiding the use of harsh conditions and toxic catalysts, (2) providing strict control of regio-and stereo-selectivity and (3) high efficiency. This review describes the in vivo and in vitro glycosylation of natural organic compounds using glycosyltransferases, focusing on our investigation of enzymatic synthesis of curcumin glycosides. Our current efforts toward functional characterization of some glycosyltransferases involved in the biosynthesis of iridoids and crocin, as well as in the sugar chain elongation of quercetin glucosides, are described. Finally, I describe the relationship of the structure of sugar chains and the intestinal absorption which was investigated using chemoenzymatically synthesized quercetin glycosides.

The xyloglucan-cellulose assembly at the atomic scale.

PubMed

Hanus, Jaroslav; Mazeau, Karim

2006-05-01

The assembly of cell wall components, cellulose and xyloglucan (XG), was investigated at the atomistic scale using molecular dynamics simulations. A molecular model of a cellulose crystal corresponding to the allomorph Ibeta and exhibiting a flexible complex external morphology was employed to mimic the cellulose microfibril. The xyloglucan molecules considered were the three typical basic repeat units, differing only in the size of one of the lateral chain. All the investigated XG fragments adsorb nonspecifically onto cellulose fiber; multiple arrangements are equally probable, and every cellulose surface was capable of binding the short XG molecules. The following structural effects emerged: XG molecules that do not have any long side chains tended to adapt themselves nicely to the topology of the microfibril, forming a flat, outstretched conformation with all the sugar residues interacting with the surface. In contrast, the XG molecules, which have long side chains, were not able to adopt a flat conformation that would enable the interaction of all the XG residues with the surface. In addition to revealing the fundamental atomistic details of the XG adsorption on cellulose, the present calculations give a comprehensive understanding of the way the XG molecules can unsorb from cellulose to create a network that forms the cell wall. Our revisited view of the adsorption features of XG on cellulose microfibrils is consistent with experimental data, and a model of the network is proposed. Copyright (c) 2006 Wiley Periodicals, Inc.

Design and investigation of de Vries liquid crystals based on 5-phenyl-pyrimidine and (R,R)-2,3-epoxyhexoxy backbone

NASA Astrophysics Data System (ADS)

Sreenilayam, S. P.; Rodriguez-Lojo, D.; Panov, V. P.; Swaminathan, V.; Vij, J. K.; Panarin, Yu. P.; Gorecka, E.; Panov, A.; Stevenson, P. J.

2017-10-01

Calamitic liquid crystals based on 5-phenyl-pyrimidine derivatives have been designed, synthesized, and characterized. The 5-phenyl pyrimidine core was functionalized with a chiral (R,R)-2,3-epoxyhexoxy chain on one side and either siloxane or perfluoro terminated chains on the opposite side. The one involving a perfluorinated chain shows Sm A* phase over a wide temperature range of 82 °C, whereas the siloxane analog exhibits both Sm A* and Sm C* phases over a broad range of temperatures, and a weak first-order Sm A*-Sm C* transition is observed. For the siloxane analog, the reduction factor for the layer shrinkage R (relative to its thickness at the Sm A*-Sm C* transition temperature, TAC) is ˜0.373 , and layer shrinkage is 1.7% at a temperature of 13 °C below the TAC. This compound is considered to have "de Vries smectic" characteristics with the de Vries coefficient CdeVries of ˜0.86 on the scale of zero (maximum-layer shrinkage) to 1 (zero-layer shrinkage). A three-parameter mean-field model is introduced for the orientational distribution function (ODF) to reproduce the electro-optic properties. This model explains the experimental results and leads to the ODF, which exhibits a crossover from the sugar-loaf to diffuse-cone ODF some 3 °C above TAC.

Genetics and evolution of Yersinia pseudotuberculosis O-specific polysaccharides: a novel pattern of O-antigen diversity

PubMed Central

Kenyon, Johanna J.; Cunneen, Monica M.

2017-01-01

Abstract O-antigen polysaccharide is a major immunogenic feature of the lipopolysaccharide of Gram-negative bacteria, and most species produce a large variety of forms that differ substantially from one another. There are 18 known O-antigen forms in the Yersinia pseudotuberculosis complex, which are typical in being composed of multiple copies of a short oligosaccharide called an O unit. The O-antigen gene clusters are located between the hemH and gsk genes, and are atypical as 15 of them are closely related, each having one of five downstream gene modules for alternative main-chain synthesis, and one of seven upstream modules for alternative side-branch sugar synthesis. As a result, many of the genes are in more than one gene cluster. The gene order in each module is such that, in general, the earlier a gene product functions in O-unit synthesis, the closer the gene is to the 5΄ end for side-branch modules or the 3΄ end for main-chain modules. We propose a model whereby natural selection could generate the observed pattern in gene order, a pattern that has also been observed in other species. PMID:28364730

1. View looking east from sand bar on west side ...

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

1. View looking east from sand bar on west side of bridge, upstream in the bed of Sugar Creek. West elevation of the bridge - Vigo County Bridge No. 139, Spanning Sugar Creek at Seventy-fourth Place, Terre Haute, Vigo County, IN

Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents

PubMed Central

Zhao, Huiping; Donnelly, Alison C.; Kusuma, Bhaskar R.; Brandt, Gary E. L.; Brown, Douglas; Rajewski, Roger A.; Vielhauer, George; Holzbeierlein, Jeffrey; Cohen, Mark S.; Blagg, Brian S. J.

2011-01-01

Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition. PMID:21553822

Sugar fatty acid esters inhibit biofilm formation by food-borne pathogenic bacteria

PubMed Central

Furukawa, Soichi; Akiyoshi, Yuko; O’Toole, George A.; Ogihara, Hirokazu; Morinaga, Yasushi

2010-01-01

Effects of food additives on biofilm formation by food-borne pathogenic bacteria were investigated. Thirty-three potential food additives and 3 related compounds were added to the culture medium at concentrations from 0.001 to 0.1% (w/w), followed by inoculation and cultivation of five biofilm-forming bacterial strains for the evaluation of biofilm formation. Among the tested food additives, 21 showed inhibitory effects of biofilm formation by Staphylococcus aureus and Escherichia coli, and in particular, sugar fatty acid esters showed significant anti-biofilm activity. Sugar fatty acid esters with long chain fatty acid residues (C14-16) exerted their inhibitory effect at the concentration of 0.001%(w/w), but bacterial growth was not affected at this low concentration. Activities of the sugar fatty acid esters positively correlated with the increase of the chain length of the fatty acid residues. Sugar fatty acid esters inhibited the initial attachment of the Staphylococcus aureus cells to the abiotic surface. Sugar fatty acid esters with long chain fatty acid residues (C14-16) also inhibited biofilm formation by Streptococcus mutans and Listeria monocytogenes at 0.01%(w/w), while the inhibition of biofilm formation by Pseudomonas aeruginosa required the addition of a far higher concentration (0.1%(w/w)) of the sugar fatty acid esters. PMID:20089325

Secondary cell-wall assembly in flax phloem fibres: role of galactans.

PubMed

Gorshkova, Tatyana; Morvan, Claudine

2006-01-01

Non-lignified fibre cells (named gelatinous fibres) are present in tension wood and the stems of fibre crops (such as flax and hemp). These cells develop a very thick S2 layer within the secondary cell wall, which is characterised by (1) cellulose microfibrils largely parallel to the longitudinal axis of the cell, and (2) a high proportion of galactose-containing polymers among the non-cellulosic polysaccharides. In this review, we focus on the role of these polymers in the assembly of gelatinous fibres of flax. At the different stages of fibre development, we analyse in detail data based on sugar composition, linkages of pectic polymers, and immunolocalisation of the beta-(1-->4)-galactans. These data indicate that high molecular-mass gelatinous galactans accumulate in specialised Golgi-derived vesicles during fibre cell-wall thickening. They consist of RG-I-like polymers with side chains of beta-(1-->4)-linked galactose. Most of them are short, but there are also long chains containing up to 28 galactosyl residues. At fibre maturity, two types of cross-linked galactans are identified, a C-L structure that resembles the part of soluble galactan with long side chains and a C-S structure with short chains. Different possibilities for soluble galactan to give rise to C-L and C-S are analysed. In addition, we discuss the prospect for the soluble galactan in preventing the newly formed cellulose chains from completing immediate crystallisation. This leads to a hypothesis that firstly the secretion of soluble galactans plays a role in the axial orientation of cellulose microfibrils, and secondly the remodelling and cross-linking of pectic galactans are linked to the dehydration and the assembly of S2 layer.

Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity.

PubMed

Swanson, Michael D; Boudreaux, Daniel M; Salmon, Loïc; Chugh, Jeetender; Winter, Harry C; Meagher, Jennifer L; André, Sabine; Murphy, Paul V; Oscarson, Stefan; Roy, René; King, Steven; Kaplan, Mark H; Goldstein, Irwin J; Tarbet, E Bart; Hurst, Brett L; Smee, Donald F; de la Fuente, Cynthia; Hoffmann, Hans-Heinrich; Xue, Yi; Rice, Charles M; Schols, Dominique; Garcia, J Victor; Stuckey, Jeanne A; Gabius, Hans-Joachim; Al-Hashimi, Hashim M; Markovitz, David M

2015-10-22

A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity, while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code. Copyright © 2015 Elsevier Inc. All rights reserved.

Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity

PubMed Central

Swanson, Michael D.; Boudreaux, Daniel M.; Salmon, Loïc; Chugh, Jeetender; Winter, Harry C.; Meagher, Jennifer L.; André, Sabine; Murphy, Paul V.; Oscarson, Stefan; Roy, René; King, Steven; Kaplan, Mark H.; Goldstein, Irwin J.; Tarbet, E. Bart; Hurst, Brett L.; Smee, Donald F.; de la Fuente, Cynthia; Hoffmann, Hans-Heinrich; Xue, Yi; Rice, Charles M.; Schols, Dominique; Garcia, J. Victor; Stuckey, Jeanne A.; Gabius, Hans-Joachim; Al-Hashimi, Hashim M.; Markovitz, David M.

2015-01-01

Summary A key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code. PMID:26496612

Free energy surfaces for the interaction of D-glucose with planar aromatic groups in aqueous solution

NASA Astrophysics Data System (ADS)

Wohlert, Jakob; Schnupf, Udo; Brady, John W.

2010-10-01

Multidimensional potentials of mean force for the interactions in aqueous solution of both anomers of D-glucopyranose with two planar aromatic molecules, indole and para-methyl-phenol, have been calculated using molecular dynamics simulations with umbrella sampling and were subsequently used to estimate binding free energies. Indole and para-methyl-phenol serve as models for the side chains of the amino acids tryptophan and tyrosine, respectively. In all cases, a weak affinity between the glucose molecules and the flat aromatic surfaces was found. The global minimum for these interactions was found to be for the case when the pseudoplanar face of β-D-glucopyranose is stacked against the planar surfaces of the aromatic residues. The calculated binding free energies are in good agreement with both experiment and previous simulations. The multidimensional free energy maps suggest a mechanism that could lend kinetic stability to the complexes formed by sugars bound to sugar-binding proteins.

Process development of short-chain polyols synthesis from corn stover by combination of enzymatic hydrolysis and catalytic hydrogenolysis.

PubMed

Fang, Zhen-Hong; Zhang, Jian; Lu, Qi-Ming; Bao, Jie

2014-09-01

Currently short-chain polyols such as ethanediol, propanediol, and butanediol are produced either from the petroleum feedstock or from the starch-based food crop feedstock. In this study, a combinational process of enzymatic hydrolysis with catalytic hydrogenolysis for short-chain polyols production using corn stover as feedstock was developed. The enzymatic hydrolysis of the pretreated corn stover was optimized to produce stover sugars at the minimum cost. Then the stover sugars were purified and hydrogenolyzed into polyols products catalyzed by Raney nickel catalyst. The results show that the yield of short-chain polyols from the stover sugars was comparable to that of the corn-based glucose. The present study provided an important prototype for polyols production from lignocellulose to replace the petroleum- or corn-based polyols for future industrial applications.

Genomic analysis of branched chain fatty acid and acyl sugar production in Solanum pennellii and Nicotiana benthamiana

USDA-ARS?s Scientific Manuscript database

Acyl sugars are extracellular epidermal lipids that are exuded from glandular trichomes and coat the aerial organs of many species in the Solanaceae. These highly viscous surfactants, which often contain branched-chain fatty acids (BCFA), play an important defensive role against pest and insects. ...

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits

PubMed Central

Gaudier-Diaz, Monica M.; Weinhold, Kellie R.; DeVries, A. Courtney

2017-01-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors. PMID:27933449

Clearing the fog: a review of the effects of dietary omega-3 fatty acids and added sugars on chemotherapy-induced cognitive deficits.

PubMed

Orchard, Tonya S; Gaudier-Diaz, Monica M; Weinhold, Kellie R; Courtney DeVries, A

2017-02-01

Cancer treatments such as chemotherapy have been an important part of extending survival in women diagnosed with breast cancer. However, chemotherapy can cause potentially toxic side effects in the brain that impair memory, verbal fluency, and processing speed in up to 30% of women treated. Women report that post-chemotherapy cognitive deficits negatively impact quality of life and may last up to ten years after treatment. Mechanisms underlying these cognitive impairments are not fully understood, but emerging evidence suggests that chemotherapy induces structural changes in the brain, produces neuroinflammation, and reduces adult hippocampal neurogenesis. Dietary approaches that modify inflammation and neurogenesis are promising strategies for reducing chemotherapy-induced cognitive deficits in breast cancer survivors. In this review, we describe the cognitive and neuronal side effects associated with commonly used chemotherapy treatments for breast cancer, and we focus on the often opposing actions of omega-3 fatty acids and added sugars on cognitive function, neuroinflammation, and adult hippocampal neurogenesis. Omega-3 fatty acids administered concurrently with doxorubicin chemotherapy have been shown to prevent depressive-like behaviors and reduce neuroinflammation, oxidative stress, and neural apoptosis in rodent models. In contrast, diets high in added sugars may interact with n-3 FAs to diminish their anti-inflammatory activity or act independently to increase neuroinflammation, reduce adult hippocampal neurogenesis, and promote cognitive deficits. We propose that a diet rich in long-chain, marine-derived omega-3 fatty acids and low in added sugars may be an ideal pattern for preventing or alleviating neuroinflammation and oxidative stress, thereby protecting neurons from the toxic effects of chemotherapy. Research testing this hypothesis could lead to the identification of modifiable dietary choices to reduce the long-term impact of chemotherapy on the cognitive functions that are important to quality of life in breast cancer survivors.

Characterization of citrus pectin samples extracted under different conditions: influence of acid type and pH of extraction

PubMed Central

Kaya, Merve; Sousa, António G.; Crépeau, Marie-Jeanne; Sørensen, Susanne O.; Ralet, Marie-Christine

2014-01-01

Background and Aims Pectin is a complex macromolecule, the fine structure of which is influenced by many factors. It is used as a gelling, thickening and emulsifying agent in a wide range of applications, from food to pharmaceutical products. Current industrial pectin extraction processes are based on fruit peel, a waste product from the juicing industry, in which thousands of tons of citrus are processed worldwide every year. This study examines how pectin components vary in relation to the plant source (orange, lemon, lime, grapefruit) and considers the influence of extraction conditions on the chemical and macromolecular characteristics of pectin samples. Methods Citrus peel (orange, lemon, lime and grapefruit) from a commercial supplier was used as raw material. Pectin samples were obtained on a bulk plant scale (kilograms; harsh nitric acid, mild nitric acid and harsh oxalic acid extraction) and on a laboratory scale (grams; mild oxalic acid extraction). Pectin composition (acidic and neutral sugars) and physicochemical properties (molar mass and intrinsic viscosity) were determined. Key Results Oxalic acid extraction allowed the recovery of pectin samples of high molecular weight. Mild oxalic acid-extracted pectins were rich in long homogalacturonan stretches and contained rhamnogalacturonan I stretches with conserved side chains. Nitric acid-extracted pectins exhibited lower molecular weights and contained rhamnogalacturonan I stretches encompassing few and/or short side chains. Grapefruit pectin was found to have short side chains compared with orange, lime and lemon. Orange and grapefruit pectin samples were both particularly rich in rhamnogalacturonan I backbones. Conclusions Structural, and hence macromolecular, variations within the different citrus pectin samples were mainly related to their rhamnogalacturonan I contents and integrity, and, to a lesser extent, to the length of their homogalacturonan domains. PMID:25081519

Quantifying side-chain conformational variations in protein structure

PubMed Central

Miao, Zhichao; Cao, Yang

2016-01-01

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

Quantifying side-chain conformational variations in protein structure

NASA Astrophysics Data System (ADS)

Miao, Zhichao; Cao, Yang

2016-11-01

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

Quantifying side-chain conformational variations in protein structure.

PubMed

Miao, Zhichao; Cao, Yang

2016-11-15

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

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

PubMed

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

2018-04-19

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

From Comb-like Polymers to Bottle-Brushes

NASA Astrophysics Data System (ADS)

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

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

Comparison of four glycosyl residue composition methods for effectiveness in detecting sugars from cell walls of dicot and grass tissues.

PubMed

Biswal, Ajaya K; Tan, Li; Atmodjo, Melani A; DeMartini, Jaclyn; Gelineo-Albersheim, Ivana; Hunt, Kimberly; Black, Ian M; Mohanty, Sushree S; Ryno, David; Wyman, Charles E; Mohnen, Debra

2017-01-01

The effective use of plant biomass for biofuel and bioproduct production requires a comprehensive glycosyl residue composition analysis to understand the different cell wall polysaccharides present in the different biomass sources. Here we compared four methods side-by-side for their ability to measure the neutral and acidic sugar composition of cell walls from herbaceous, grass, and woody model plants and bioenergy feedstocks. Arabidopsis, Populus , rice, and switchgrass leaf cell walls, as well as cell walls from Populus wood, rice stems, and switchgrass tillers, were analyzed by (1) gas chromatography-mass spectrometry (GC-MS) of alditol acetates combined with a total uronic acid assay; (2) carbodiimide reduction of uronic acids followed by GC-MS of alditol acetates; (3) GC-MS of trimethylsilyl (TMS) derivatives; and (4) high-pressure, anion-exchange chromatography (HPAEC). All four methods gave comparable abundance ranking of the seven neutral sugars, and three of the methods were able to quantify unique acidic sugars. The TMS, HPAEC, and carbodiimide methods provided comparable quantitative results for the specific neutral and acidic sugar content of the biomass, with the TMS method providing slightly greater yield of specific acidic sugars and high total sugar yields. The alditol acetate method, while providing comparable information on the major neutral sugars, did not provide the requisite quantitative information on the specific acidic sugars in plant biomass. Thus, the alditol acetate method is the least informative of the four methods. This work provides a side-by-side comparison of the efficacy of four different established glycosyl residue composition analysis methods in the analysis of the glycosyl residue composition of cell walls from both dicot (Arabidopsis and Populus ) and grass (rice and switchgrass) species. Both primary wall-enriched leaf tissues and secondary wall-enriched wood/stem tissues were analyzed for mol% and mass yield of the non-cellulosic sugars. The TMS, HPAEC, and carbodiimide methods were shown to provide comparable quantitative data on the nine neutral and acidic sugars present in all plant cell walls.

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

NASA Astrophysics Data System (ADS)

Porter, Stephen Christopher

1999-10-01

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

Changes in conformational dynamics of basic side chains upon protein–DNA association

PubMed Central

Esadze, Alexandre; Chen, Chuanying; Zandarashvili, Levani; Roy, Sourav; Pettitt, B. Montgometry; Iwahara, Junji

2016-01-01

Basic side chains play major roles in recognition of nucleic acids by proteins. However, dynamic properties of these positively charged side chains are not well understood. In this work, we studied changes in conformational dynamics of basic side chains upon protein–DNA association for the zinc-finger protein Egr-1. By nuclear magnetic resonance (NMR) spectroscopy, we characterized the dynamics of all side-chain cationic groups in the free protein and in the complex with target DNA. Our NMR order parameters indicate that the arginine guanidino groups interacting with DNA bases are strongly immobilized, forming rigid interfaces. Despite the strong short-range electrostatic interactions, the majority of the basic side chains interacting with the DNA phosphates exhibited high mobility, forming dynamic interfaces. In particular, the lysine side-chain amino groups exhibited only small changes in the order parameters upon DNA-binding. We found a similar trend in the molecular dynamics (MD) simulations for the free Egr-1 and the Egr-1–DNA complex. Using the MD trajectories, we also analyzed side-chain conformational entropy. The interfacial arginine side chains exhibited substantial entropic loss upon binding to DNA, whereas the interfacial lysine side chains showed relatively small changes in conformational entropy. These data illustrate different dynamic characteristics of the interfacial arginine and lysine side chains. PMID:27288446

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

Lenné, T.; Kent, B.; Koster, K.L.

Small angle X-ray scattering is used to study the effects of sugars on membranes during dehydration. Previous work has shown that the bilayer and chain-chain repeat spacings of DPPC bilayers are relatively unaffected by the presence of sugars. In this work we present a preliminary analysis of the electron density profiles of DPPC in the presence of sugars at low hydration. The difficulties of determining the correct phasing are discussed. Sugars and other small solutes have been shown to have an important role in improving the tolerance of a range of species to desiccation and freezing. In particular it hasmore » been shown that sugars can stabilize membranes in the fluid membrane phase during dehydration, and in the fully dehydrated state. Equivalently, at a particular hydration, the presence of sugars lowers the transition temperature between the fluid and gel phases. There are two competing models for explaining the effects of sugars on membrane phase transition temperatures. One, designated the water replacement hypothesis (WRH) states that sugars hydrogen bond to phospholipid headgroups, thus hindering the fluid-gel phase transition. One version of this model suggests that certain sugars (such as trehalose) achieve the measured effects by inserting between the phospholipid head groups. An alternative model explains the observed effects of sugars in terms of the sugars effect on the hydration repulsion that develops between opposing membranes during dehydration. The hydration repulsion leads to a lateral compressive stress in the bilayer which squeezes adjacent lipids more closely together, resulting in a transition to the gel phase. When sugars are present, their osmotic and volumetric effects reduce the hydration repulsion, reduce the compressive stress in the membranes, and therefore tend to maintain the average lateral separation between lipids. This model is called the hydration forces explanation (HFE). We recently showed that neither mono- nor di-saccharides affect the average distance between lipid chains in the bilayer, supporting the predictions of the HFE. In this paper we further investigate the effects of sugars on membrane structure by conducting electron density analysis of recent data. This preliminary analysis sheds additional light onto the effects of sugars on membrane structure.« less

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

NASA Technical Reports Server (NTRS)

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

1986-01-01

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

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.

Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals.

PubMed

Maynard, Jason C; Burlingame, Alma L; Medzihradszky, Katalin F

2016-11-01

Intracellular GlcNAcylation of Ser and Thr residues is a well-known and widely investigated post-translational modification. This post-translational modification has been shown to play a significant role in cell signaling and in many regulatory processes within cells. O-GlcNAc transferase is the enzyme responsible for glycosylating cytosolic and nuclear proteins with a single GlcNAc residue on Ser and Thr side-chains. Here we report that the same enzyme may also be responsible for S-GlcNAcylation, i.e. for linking the GlcNAc unit to the peptide by modifying a cysteine side-chain. We also report that O-GlcNAcase, the enzyme responsible for removal of O-GlcNAcylation does not appear to remove the S-linked sugar. Such Cys modifications have been detected and identified in mouse and rat samples. This work has established the occurrence of 14 modification sites assigned to 11 proteins unambiguously. We have also identified S-GlcNAcylation from human Host Cell Factor 1 isolated from HEK-cells. Although these site assignments are primarily based on electron-transfer dissociation mass spectra, we also report that S-linked GlcNAc is more stable under collisional activation than O-linked GlcNAc derivatives. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

3. RW Meyer Sugar Mill: 18761889. Sorghum pan and boiling ...

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

3. RW Meyer Sugar Mill: 1876-1889. Sorghum pan and boiling range flue. Manufactured by John Nott & Co., Honolulu, Hawaii, 1878. View: South side of sorghum pan and boiling range flue. In the sorghum pan heat was applied to the cane juice to clarify it, evaporate its water content, and concentrate the sugar crystals. Hot gasses moved through the flue underneath the entire copper bottom of the sorghum pan from the furnace (east) end to the smokestack (west) end of the boiling range. The sorghum pan sides are of redwood. The flue is built of fire-brick, masonry, and portland cement. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

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

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

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

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

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

PubMed

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

2018-05-08

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

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

DOE PAGES

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

2018-04-24

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

Changes in conformational dynamics of basic side chains upon protein-DNA association.

PubMed

Esadze, Alexandre; Chen, Chuanying; Zandarashvili, Levani; Roy, Sourav; Pettitt, B Montgometry; Iwahara, Junji

2016-08-19

Basic side chains play major roles in recognition of nucleic acids by proteins. However, dynamic properties of these positively charged side chains are not well understood. In this work, we studied changes in conformational dynamics of basic side chains upon protein-DNA association for the zinc-finger protein Egr-1. By nuclear magnetic resonance (NMR) spectroscopy, we characterized the dynamics of all side-chain cationic groups in the free protein and in the complex with target DNA. Our NMR order parameters indicate that the arginine guanidino groups interacting with DNA bases are strongly immobilized, forming rigid interfaces. Despite the strong short-range electrostatic interactions, the majority of the basic side chains interacting with the DNA phosphates exhibited high mobility, forming dynamic interfaces. In particular, the lysine side-chain amino groups exhibited only small changes in the order parameters upon DNA-binding. We found a similar trend in the molecular dynamics (MD) simulations for the free Egr-1 and the Egr-1-DNA complex. Using the MD trajectories, we also analyzed side-chain conformational entropy. The interfacial arginine side chains exhibited substantial entropic loss upon binding to DNA, whereas the interfacial lysine side chains showed relatively small changes in conformational entropy. These data illustrate different dynamic characteristics of the interfacial arginine and lysine side chains. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

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

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

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

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

SCit: web tools for protein side chain conformation analysis.

PubMed

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

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

Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin.

PubMed

Misaizu, T; Matsuki, S; Strickland, T W; Takeuchi, M; Kobata, A; Takasaki, S

1995-12-01

To elucidate the role of the branched structure of sugar chains of human erythropoietin (EPO) in the expression of in vivo activity, the pharmacokinetic profile of a less active recombinant human EPO sample (EPO-bi) enriched with biantennary sugar chains was compared with that of a highly active control EPO sample enriched with tetraantennary sugar chains. After an intravenous injection in rats, 125I-EPO-bi disappeared from the plasma with 3.2 times greater total body clearance (Cltot) than control 125I-EPO. Whole-body autoradiography after 20 minutes of administration indicated that the overall distribution of radioactivity is similar, but 125I-EPO-bi showed a higher level of radioactivity in the kidneys than control 125I-EPO. Quantitative determination of radioactivity in the tissues also indicated that radioactivity of 125I-EPO-bi in the kidneys was two times higher than that of control 125I-EPO. The difference in plasma disappearance between 125I-EPO-bi and control 125I-EPO was not observed in bilaterally nephrectomized rats. The distribution of 125I-EPO-bi to bone marrow and spleen was similarly inhibited by simultaneous injection of excess amounts of either the nonlabeled EPO-bi or control EPO. These results indicate that the low in vivo biologic activity of EPO-bi results from rapid clearance from the systemic circulation by renal handling. Thus, the well-branched structure of the N-linked sugar chain of EPO is suggested to play an important role in maintaining its higher plasma level, which guarantees an effective transfer to target organs and stimulation of erythroid progenitor cells.

Amino and Acetamide Functional Group Effects on the Ionization and Fragmentation of Sugar Chains in Positive-Ion Mass Spectrometry

NASA Astrophysics Data System (ADS)

Yamagaki, Tohru; Sugahara, Kohtaro; Watanabe, Takehiro

2014-01-01

To elucidate the influence of amino (-NH2) and acetamide (-NHCOCH3, -NAc) groups in sugar chains on their ionization and fragmentation, cycloamyloses (cyclodextrins, CyDs) and lacto-oligosaccharide are analyzed by MALDI TOF/TOF and ESI Q-TOF mass spectrometry. CyD derivatives substituted by amino or acetamide groups are ideal analytes to extract the function group effects, which are amino-CyD with one hexosamine (HexNH2) and acetamide-CyD with one N-acetyl hexosamine (HexNAc). Interestingly, the relative ion intensities and isotope-like patterns in their product ion spectra depend on the functional groups and ion forms of sugar chains. Consequently, the results indicate that a proton (H+) localizes on the amino group of the amino sugar, and that the proton (H+) induces their fragmentation. Sodium cation (Na+) attachment is independent from amino group and exerts no influence on their fragmentation patterns in amino group except for mono- and disaccharide fragment ions because there is the possibility of the reducing end effect. In contrast, a sodium cation localizes much more frequently on the acetamide group in acetamide-CyDs because the chemical species with HexNAc are stable. Thus, their ions with HexNAc are abundant. These results are consistent with the fragmentation of lacto-neo- N-tetraose and maltotetraose, suggesting that a sodium cation generally localizes much more frequently on the acetamide group in sugar chains.

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 building block, and functionalization densities. PMID:18341334

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

PubMed

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

2014-01-01

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

Side-chain mobility in the folded state of Myoglobin

NASA Astrophysics Data System (ADS)

Lammert, Heiko; Onuchic, Jose

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

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

PubMed

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

2012-01-01

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

Muscular Dystrophy with Ribitol-Phosphate Deficiency: A Novel Post-Translational Mechanism in Dystroglycanopathy

PubMed Central

Kanagawa, Motoi; Toda, Tatsushi

2017-01-01

Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness. In the early 2000s, a new classification of muscular dystrophy, dystroglycanopathy, was established. Dystroglycanopathy often associates with abnormalities in the central nervous system. Currently, at least eighteen genes have been identified that are responsible for dystroglycanopathy, and despite its genetic heterogeneity, its common biochemical feature is abnormal glycosylation of alpha-dystroglycan. Abnormal glycosylation of alpha-dystroglycan reduces its binding activities to ligand proteins, including laminins. In just the last few years, remarkable progress has been made in determining the sugar chain structures and gene functions associated with dystroglycanopathy. The normal sugar chain contains tandem structures of ribitol-phosphate, a pentose alcohol that was previously unknown in humans. The dystroglycanopathy genes fukutin, fukutin-related protein (FKRP), and isoprenoid synthase domain-containing protein (ISPD) encode essential enzymes for the synthesis of this structure: fukutin and FKRP transfer ribitol-phosphate onto sugar chains of alpha-dystroglycan, and ISPD synthesizes CDP-ribitol, a donor substrate for fukutin and FKRP. These findings resolved long-standing questions and established a disease subgroup that is ribitol-phosphate deficient, which describes a large population of dystroglycanopathy patients. Here, we review the history of dystroglycanopathy, the properties of the sugar chain structure of alpha-dystroglycan, dystroglycanopathy gene functions, and therapeutic strategies. PMID:29081423

Endoglycosidase and glycoamidase release of N-linked oligosaccharides.

PubMed

Freeze, H H

2001-05-01

Carbohydrate chain modifications are often used to monitor glycoprotein movement through the secretory pathway. This is because stepwise sugar-chain processing is unidirectional and generally corresponds to the forward or anterograde movement of proteins. This unit offers a group of techniques that will help analyze the general structure of carbohydrate chains on a protein and, therefore, oligosaccharide processing mileposts. The sugar chains themselves are not analyzed, but their presence and structure are inferred from gel mobility differences after one or more enzymatic digestions. This approach is most often used in combination with [35S]Met pulse-chase metabolic labeling protocols, but they can be applied to any suitably labeled protein (e.g., biotinylated or 125I-labeled).

SCit: web tools for protein side chain conformation analysis

PubMed Central

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

2004-01-01

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

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.

Steric interactions determine side-chain conformations in protein cores.

PubMed

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

2016-09-01

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

Economic feasibility of the sugar beet-to-ethylene value chain.

PubMed

Althoff, Jeroen; Biesheuvel, Kees; De Kok, Ad; Pelt, Henk; Ruitenbeek, Matthijs; Spork, Ger; Tange, Jan; Wevers, Ronald

2013-09-01

As part of a long-term strategy toward renewable feedstock, a feasibility study into options for the production of bioethylene by integrating the sugar beet-to-ethanol-to-ethylene value chain. Seven business cases were studied and tested for actual economic feasibility of alternative sugar-to-ethanol-to-ethylene routes in comparison to fossil-fuel alternatives. An elaborate model was developed to assess the relevant operational and financial aspects of each business case. The calculations indicate that bioethylene from sugar beet is not commercially viable under current market conditions. In light of expected global energy and feedstock prices it is also reasonable to expect that this will not change in the near future. To consider biorenewable sources as starting material, they need to be low in cost (compared to sugar beets) and also require less capital and energy-intensive methods for the conversion to chemicals. In general, European sugar prices will be too high for many chemical applications. Future efforts for in sugar-to-chemicals routes should, therefore, focus on integrated process routes and process intensification and/or on products that contain a significant part of the original carbohydrate backbone. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-knock quality of sugar derived levulinic esters and cyclic ethers

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

Tian, Miao; McCormick, Robert L.; Luecke, Jon

Here, the objective of this paper is to investigate the anti-knock quality of sugar-derived levulinic esters (methyl levulinate (ML) and ethyl levulinate (EL)) and cyclic ethers (furfuryl ethyl ether (FEE) and ethyl tetrahydrofurfuryl ether (ETE)). To this end, combustion experiments were carried out in both an engine and a constant volume autoignition device. The results from both apparati demonstrate that ML, EL and FEE have superior anti-knock quality than the reference Euro95 gasoline. ETE, conversely, performed markedly worse than the reference fuel on both setups and might therefore be a more appropriate fuel for compression ignition engines. The main reasonmore » of the distinctions in anti-knock quality can be found in the molecular structure of the neat biofuels. ML and EL are levulinic esters, with a ketone (C=O) functionality and an ester (C(=O)-O) group on the carbon chain. They can readily produce stable intermediates during the auto-ignition process, thereby slowing down the overall reaction rate. The unsaturated cyclic ether (FEE) has very strong ring C-H bonds. However, the saturated cyclic ether (ETE) has weak ring C-H bonds, which facilitate more readily ring opening reactions. Long side chains on the cyclic ethers further accelerate the reaction rate. Importantly for future research, our results suggest that IQT and engine experiments are interchangeable setups with respect to qualitative anti-knock quality evaluation of novel compounds.« less

Anti-knock quality of sugar derived levulinic esters and cyclic ethers

DOE PAGES

Tian, Miao; McCormick, Robert L.; Luecke, Jon; ...

2017-04-22

Here, the objective of this paper is to investigate the anti-knock quality of sugar-derived levulinic esters (methyl levulinate (ML) and ethyl levulinate (EL)) and cyclic ethers (furfuryl ethyl ether (FEE) and ethyl tetrahydrofurfuryl ether (ETE)). To this end, combustion experiments were carried out in both an engine and a constant volume autoignition device. The results from both apparati demonstrate that ML, EL and FEE have superior anti-knock quality than the reference Euro95 gasoline. ETE, conversely, performed markedly worse than the reference fuel on both setups and might therefore be a more appropriate fuel for compression ignition engines. The main reasonmore » of the distinctions in anti-knock quality can be found in the molecular structure of the neat biofuels. ML and EL are levulinic esters, with a ketone (C=O) functionality and an ester (C(=O)-O) group on the carbon chain. They can readily produce stable intermediates during the auto-ignition process, thereby slowing down the overall reaction rate. The unsaturated cyclic ether (FEE) has very strong ring C-H bonds. However, the saturated cyclic ether (ETE) has weak ring C-H bonds, which facilitate more readily ring opening reactions. Long side chains on the cyclic ethers further accelerate the reaction rate. Importantly for future research, our results suggest that IQT and engine experiments are interchangeable setups with respect to qualitative anti-knock quality evaluation of novel compounds.« less

1H, 15N and 13C backbone and side-chain resonance assignments of a family 32 carbohydrate-binding module from the Clostridium perfringens NagH.

PubMed

Grondin, Julie M; Chitayat, Seth; Ficko-Blean, Elizabeth; Boraston, Alisdair B; Smith, Steven P

2012-10-01

The Gram-positive anaerobe Clostridium perfringens is an opportunistic bacterial pathogen that secretes a battery of enzymes involved in glycan degradation. These glycoside hydrolases are thought to be involved in turnover of mucosal layer glycans, and in the spread of major toxins commonly associated with the development of gastrointestinal diseases and gas gangrene in humans. These enzymes employ multi-modularity and carbohydrate-binding function to degrade extracellular eukaryotic host sugars. Here, we report the full (1)H, (15)N and (13)C chemical shift resonance assignments of the first family 32 carbohydrate-binding module from NagH, a secreted family 84 glycoside hydrolase.

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.

15. RW Meyer Sugar Mill: 18761889. Sorghum pan and boiling ...

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

15. RW Meyer Sugar Mill: 1876-1889. Sorghum pan and boiling range flue. Manufactured by John Nott & Co., Honolulu, Hawaii, 1878. View: North side of sorghum pan and boiling range flue, with furnace-end in background. In the sorghum pan heat was applied to the cane juice to clarify it, evaporate its water content, and concentrate the sugar crystals. Hot gasses moved through the flue underneath the entire copper bottom of the sorghum pan from the furnace end (in background) to the smokestack end (in foreground). After the hot cane juice moved through the separate compartments until it reached the final compartment (now missing two sides) where it was drawn out from the copper lip in the corner. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

9. RW Meyer Sugar Mill: 18761889. Locomotivetype, firetube, portable boiler, ...

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

9. RW Meyer Sugar Mill: 1876-1889. Locomotive-type, fire-tube, portable boiler, No. 1 model. Manufactured by Ames Iron Works, Oswego, New York, 1879. 120 lbs/sq. inch working pressure, 66 sq. ft. heating surface in tubes. View: from side. The boiler provided steam for steam engine which in turn powered the mill's centrifugals. The section on the left side included the firebox with its surrounding water-legs. The fluted chimney-type structure is the steam port, safety valve, and whistle. Column projecting from side was part of steam pressure and water gauge. Pipe running above boiler carried steam to the engine. Pipe running below boiler provided the boiler feed-water. Cylindrical section included 22 fire-tube surrounded by water. The far right ... - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

Protein side chain conformation predictions with an MMGBSA energy function.

PubMed

Gaillard, Thomas; Panel, Nicolas; Simonson, Thomas

2016-06-01

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2014-08-28

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

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

Development of molecularly imprinted polymer-based field effect transistor for sugar chain sensing

NASA Astrophysics Data System (ADS)

Nishitani, Shoichi; Kajisa, Taira; Sakata, Toshiya

2017-04-01

In this study, we developed a molecularly imprinted polymer-based field-effect transistor (MIP-gate FET) for selectively detecting sugar chains in aqueous media, focusing on 3‧-sialyllactose (3SLac) and 6‧-sialyllactose (6SLac). The FET biosensor enables the detection of small molecules as long as they have intrinsic charges. Additionally, the MIP gels include the template for the target molecule, which is selectively trapped without requiring enzyme-target molecule reaction. The MIP gels were synthesized on the gate surface of the FET device, including phenylboronic acid (PBA), which enables binding to sugar chains. Firstly, the 3SLac-MIP-gate FET quantitatively detected 3SLac at µM levels. This is because the FET device recognized the change in molecular charges on the basis of PBA-3SLac binding in the MIP gel. Moreover, 3SLac was selectively detected using the 3SLac- and 6SLac-MIP-gate FETs to some extent, where the detecting signal from the competent was suppressed by 40% at maximum. Therefore, a platform based on the MIP-coupled FET biosensor is suitable for a selective biosensing system in an enzyme-free manner, which can be applied widely in medical fields. However, we need to further improve the selectivity of MIP-gate FETs to discriminate more clearly between similar structures of sugar chains such as 3SLac and 6SLac.

Use of Scented Sugar Bait Stations to Track Mosquito-Borne Arbovirus Transmission in California

PubMed Central

LOTHROP, HUGH D.; WHEELER, SARAH S.; FANG, YING; REISEN, WILLIAM K.

2012-01-01

Laboratory and field research was conducted to determine if Culex tarsalis Coquillett expectorated West Nile virus (WNV) during sugar feeding and if a lure or bait station could be developed to exploit this behavior for WNV surveillance. Experimentally infected Cx. tarsalis repeatedly expectorated WNV onto filter paper strips and into vials with wicks containing sucrose that was readily detectable by a quantitative reverse transcriptase-polymerase chain reaction assay. Few females (33%, n = 27) became infected by imbibing sugar solutions spiked with high concentrations (107 plaque forming units/ml) of WNV, indicating sugar feeding stations probably would not be a source of WNV infection. In nature, sugar bait stations scented with the floral attractant phenyl acetaldehyde tracked WNV transmission activity in desert but not urban or agricultural landscapes in California. When deployed in areas of the Coachella Valley with WNV activity during the summer of 2011, 27 of 400 weekly sugar samples (6.8%) tested positive for WNV RNA by reverse transcriptase-polymerase chain reaction. Prevalence of positives varied spatially, but positive sugar stations were detected before concurrent surveillance measures of infection (mosquito pools) or transmission (sentinel chicken seroconversions). In contrast, sugar bait stations deployed in urban settings in Los Angeles or agricultural habits near Bakersfield in Kern County supporting WNV activity produced 1 of 90 and 0 of 60 positive weekly sugar samples, respectively. These results with sugar bait stations will require additional research to enhance bait attractancy and to understand the relationship between positive sugar stations and standard metrics of arbovirus surveillance. PMID:23270177

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.

Mexico-U.S. Relations: Issues for Congress

DTIC Science & Technology

2009-04-14

highways beyond the commercial zone. Sugar and High Fructose Corn Syrup The United States and Mexico resolved a long standing trade dispute involving...sugar and high fructose corn syrup in 2006. Mexico argued that the sugar side letter negotiated under NAFTA entitled it to ship net sugar surplus to...complained that imports of high fructose corn syrup (HFCS) sweeteners from the United States constituted dumping, and it imposed anti-dumping duties

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.

Protein-ligand docking with multiple flexible side chains

NASA Astrophysics Data System (ADS)

Zhao, Yong; Sanner, Michel F.

2008-09-01

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

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

PubMed

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

2018-02-13

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

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

PubMed

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

2017-01-19

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

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

PubMed

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

2013-10-01

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

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.

Unique anthranilic acid chemistry facilitates profiling and characterization of Ser/Thr-linked sugar chains following hydrazinolysis.

PubMed

Anumula, Kalyan Rao

2008-02-01

A novel method for the analysis of Ser/Thr-linked sugar chains was made possible by the virtue of unique anthranilic acid (AA, 2-aminobenzoic acid [2AA]) chemistry for labeling carbohydrates in aqueous salt solutions (K. R. Anumula, Anal. Biochem. 350 (2006) 1-23). The protocol for profiling of Ser/Thr carbohydrates by hydrazinolysis was made simple by eliminating intermediary isolation steps involved in a sample preparation such as desalting and various chromatographic purification schemes. A 6-h hydrazinolysis was carried out at 60 degrees C for O-linked oligosaccharides and at 95 degrees C for total oligosaccharides (N-linked with some O-linked). Following evaporation of hydrazine (<10 min), the oligosaccharides were N-acetylated and derivatized with AA in the same reaction mixture containing salts. Presumably, the glycosyl-hydrazines/hydrazones present in the mixture did not interfere with AA labeling. Because AA is the most fluorescent and highly reactive tag for labeling carbohydrates, the procedures described are suitable for the analysis of a limited amount of samples ( approximately 5 microg) by the current high-resolution high-performance liquid chromatography (HPLC) methods. HPLC conditions developed for the separation of O-linked sugar chains based on size on an amide column were satisfactory for quantitative profiling and characterization. Common O-linked sugar chains found in fetuin, equine chorionic gonadotropin, and glycophorin can be analyzed in less than 50 min. In addition, these fast profiling methods were comparable to profiling by PNGase F (peptide N-glycosidase from Flavobacterium meningosepticum) digestion in terms of time, effort, and simplicity and also were highly reproducible for routine testing. The procedures for the release of sugar chains by hydrazinolysis at the microgram level, labeling with fluorescent tag AA, and profiling by HPLC should be useful in characterization of carbohydrates found in glycoproteins.

2.2 A resolution structure analysis of two refined N-acetylneuraminyl-lactose--wheat germ agglutinin isolectin complexes.

PubMed

Wright, C S

1990-10-20

The crystal structures of complexes of isolectins 1 and 2 of wheat germ agglutinin (WGA1 and WGA2) with N-acetylneuraminyl-lactose (NeuNAc-alpha(2-3)-Gal-beta(1-4)-Glc) have been refined on the basis of data in the 8 to 2.2 A resolution range to final crystallographic R-factors of 17.2% and 15.3% (Fo greater than 1 sigma), respectively. Specific binding interactions and water association, as well as changes in conformation and mobility of the structure upon ligand binding, were compared in the two complexes. The temperature factors (B = 16.3 A2 and 18.4 A2) were found to be much lower compared with those of their respective native structures (19 to 22 A2). Residues involved in sugar binding, dimerization and in lattice contacts exhibit the largest decreases in B-value, suggesting that sugar binding reduces the overall mobility of the protein molecules in the crystal lattice. The binding mode of this sialyl-trisaccharide, an important cell receptor analogue, has been compared in the two isolectins. Only one of the two unique binding sites (4 per dimer), located in the subunit/subunit interface, is occupied in the crystals. This site, termed the "primary" binding site, contains one of the five amino acid substitutions that differentiate WGA1 and WGA2. Superposition of the refined models in each of the independent crystallographic environments indicates a close match only of the terminal non-reducing NeuNAc residue (root-mean-square delta r of 0.5 to 0.6 A). The Gal-Glc portion was found to superimpose poorly, lack electron density, and possess high atomic thermal factors. In both complexes NeuNAc is stabilized through contact with six amino acid side-chains (Ser114 and Glu115 of subunit 1 and Ser62, Tyr64, Tyr(His)66 and Tyr73 of subunit 2), involving all NeuNAc ring substituents. Refinement has allowed accurate assessment of the contact distances for four hydrogen bonds, a strong buried non-polar contact with the acetamido CH3 group and a large number of van der Waals' interactions with the three aromatic side-chains. The higher affinity of N-acetylneuraminyl-lactose observed by nuclear magnetic resonance studies for WGA1 can be explained by the more favorable binding interactions that occur when residue 66 is a Tyr. The tyrosyl side-chain provides a larger surface for van der Waals' stacking against the NeuNAc pyranose ring than His66 and a hydrogen bond contact with Gal (C2-OH), not possible in WGA2.(ABSTRACT TRUNCATED AT 400 WORDS)

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

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.

Mexico-U.S. Relations: Issues for Congress

DTIC Science & Technology

2009-05-13

zone. Sugar and High Fructose Corn Syrup The United States and Mexico resolved a long standing trade dispute involving sugar and high fructose ... high fructose corn syrup (HFCS) sweeteners from the United States constituted dumping, and it imposed anti-dumping duties for some time, until NAFTA... corn syrup in 2006. Mexico argued that the sugar side letter negotiated under NAFTA entitled it to ship net sugar surplus to the United States duty free

Coulomb repulsion in short polypeptides.

PubMed

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

2015-01-08

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

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

PubMed

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

2016-08-22

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

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

PubMed

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

2014-05-07

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

Combinatorial control of gene expression in Aspergillus niger grown on sugar beet pectin.

PubMed

Kowalczyk, Joanna E; Lubbers, Ronnie J M; Peng, Mao; Battaglia, Evy; Visser, Jaap; de Vries, Ronald P

2017-09-27

Aspergillus niger produces an arsenal of extracellular enzymes that allow synergistic degradation of plant biomass found in its environment. Pectin is a heteropolymer abundantly present in the primary cell wall of plants. The complex structure of pectin requires multiple enzymes to act together. Production of pectinolytic enzymes in A. niger is highly regulated, which allows flexible and efficient capture of nutrients. So far, three transcriptional activators have been linked to regulation of pectin degradation in A. niger. The L-rhamnose-responsive regulator RhaR controls the production of enzymes that degrade rhamnogalacturonan-I. The L-arabinose-responsive regulator AraR controls the production of enzymes that decompose the arabinan and arabinogalactan side chains of rhamnogalacturonan-II. The D-galacturonic acid-responsive regulator GaaR controls the production of enzymes that act on the polygalacturonic acid backbone of pectin. This project aims to better understand how RhaR, AraR and GaaR co-regulate pectin degradation. For that reason, we constructed single, double and triple disruptant strains of these regulators and analyzed their growth phenotype and pectinolytic gene expression in A. niger grown on sugar beet pectin.

Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

PubMed

Yoshida, K I; Honda, M; Arai, K; Hosoya, Y; Moriguchi, H; Sumi, S; Ueda, Y; Kitahara, S

1997-08-01

Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

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

PubMed

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

2012-07-01

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

Development of real-time PCR method for the detection and the quantification of a new endogenous reference gene in sugar beet "Beta vulgaris L.": GMO application.

PubMed

Chaouachi, Maher; Alaya, Akram; Ali, Imen Ben Haj; Hafsa, Ahmed Ben; Nabi, Nesrine; Bérard, Aurélie; Romaniuk, Marcel; Skhiri, Fethia; Saïd, Khaled

2013-01-01

KEY MESSAGE : Here, we describe a new developed quantitative real-time PCR method for the detection and quantification of a new specific endogenous reference gene used in GMO analysis. The key requirement of this study was the identification of a new reference gene used for the differentiation of the four genomic sections of the sugar beet (Beta vulgaris L.) (Beta, Corrollinae, Nanae and Procumbentes) suitable for quantification of genetically modified sugar beet. A specific qualitative polymerase chain reaction (PCR) assay was designed to detect the sugar beet amplifying a region of the adenylate transporter (ant) gene only from the species of the genomic section I of the genus Beta (cultivated and wild relatives) and showing negative PCR results for 7 species of the 3 other sections, 8 related species and 20 non-sugar beet plants. The sensitivity of the assay was 15 haploid genome copies (HGC). A quantitative real-time polymerase chain reaction (QRT-PCR) assay was also performed, having high linearity (R (2) > 0.994) over sugar beet standard concentrations ranging from 20,000 to 10 HGC of the sugar beet DNA per PCR. The QRT-PCR assay described in this study was specific and more sensitive for sugar beet quantification compared to the validated test previously reported in the European Reference Laboratory. This assay is suitable for GMO quantification in routine analysis from a wide variety of matrices.

Statin Side Effects: Weigh the Benefits and Risks

MedlinePlus

... your skin or eyes. Increased blood sugar or type 2 diabetes It's possible your blood sugar (blood glucose) level ... take a statin, which may lead to developing type 2 diabetes. The risk is small but important enough that ...

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

Effect of unsaturation on the absorption of ethane and ethylene in imidazolium-based ionic liquids.

PubMed

Moura, Leila; Mishra, Manas; Bernales, Varinia; Fuentealba, Patricio; Padua, Agilio A H; Santini, Catherine C; Costa Gomes, Margarida F

2013-06-20

The influence of the presence of imidazolium side chain unsaturation on the solubility of ethane and ethylene was studied in three ionic liquids: 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide-saturated alkyl side-chain in the cation; 1-methyl-3-(buten-3-yl)imidazolium bis(trifluorosulfonyl)imide-double bond in the side-chain of the cation; and 1-methyl-3-benzylimidazolium bis(trifluorosulfonyl)imide-benzyl group in the side-chain of the cation. The solubility of both gases decreases when the side-chain of the cations is functionalized with an unsaturated group. This can be explained by a less favorable enthalpy of solvation. The difference of solubility between ethane and ethylene can be explained from a balance of enthalpic and entropic factors: for the ionic liquid with the saturated alkyl side-chain and the benzyl-substituted side-chain, it is the favorable entropy of solvation that explains the larger ethylene solubility, whereas in the case of the saturated side-chain, it is the more favorable enthalpy of solvation. Molecular simulation allowed the identification of the mechanisms of solvation and the preferential solvation sites for each gas in the different ionic liquids. Simulations have shown that the entropy of solvation is more favorable when the presence of the gas weakens the cation-anion interactions or when the gas can be solvated near different sites of the ionic liquid.

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

PubMed

Rajeshwar T, Rajitha; Krishnan, Marimuthu

2017-05-25

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Molecular Structure of WlbB, a Bacterial N-Acetyltransferase Involved in the Biosynthesis of 2,3-Diacetamido-2,3-dideoxy-d-mannuronic Acid

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

Thoden, James B.; Holden, Hazel M.

2010-09-08

The pathogenic bacteria Pseudomonas aeruginosa and Bordetella pertussis contain in their outer membranes the rare sugar 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Five enzymes are required for the biosynthesis of this sugar starting from UDP-N-acetylglucosamine. One of these, referred to as WlbB, is an N-acetyltransferase that converts UDP-2-acetamido-3-amino-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NA) to UDP-2,3-diacetamido-2,3-dideoxy-D-glucuronic acid (UDP-GlcNAc3NAcA). Here we report the three-dimensional structure of WlbB from Bordetella petrii. For this analysis, two ternary structures were determined to 1.43 {angstrom} resolution: one in which the protein was complexed with acetyl-CoA and UDP and the second in which the protein contained bound CoA and UDP-GlcNAc3NA. WlbB adopts a trimericmore » quaternary structure and belongs to the L{beta}H superfamily of N-acyltransferases. Each subunit contains 27 {beta}-strands, 23 of which form the canonical left-handed {beta}-helix. There are only two hydrogen bonds that occur between the protein and the GlcNAc3NA moiety, one between O{sup {delta}1} of Asn 84 and the sugar C-3{prime} amino group and the second between the backbone amide group of Arg 94 and the sugar C-5{prime} carboxylate. The sugar C-3{prime} amino group is ideally positioned in the active site to attack the si face of acetyl-CoA. Given that there are no protein side chains that can function as general bases within the GlcNAc3NA binding pocket, a reaction mechanism is proposed for WlbB whereby the sulfur of CoA ultimately functions as the proton acceptor required for catalysis.« less

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

NASA Astrophysics Data System (ADS)

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

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

Liberal, Imperial, and Economic Motivation of U.S. Foreign Policy in the Philippines 1898-1946

DTIC Science & Technology

2008-12-01

War Department. Roosevelt had failed to push through Philippine tariff reform in each of the last four years of his administration as American sugar ...American Sugar Refining Company, who likely sponsored the attorney general’s decision.[40] Clearly Taft had to see this as the culmination of his...lined up on both sides of the debate. Industry that used sugar pressed for retention of the Philippines to keep prices down while U.S. sugar

Antibody side chain conformations are position-dependent.

PubMed

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

2018-04-01

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

35. RW Meyer Sugar Mill: 18761889. Threeroll sugar mill, oneton ...

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

35. RW Meyer Sugar Mill: 1876-1889. Three-roll sugar mill, one-ton daily processing capacity. Manufactured by Edwin Maw, Liverpool, England, ca. 1855-1870. View: Bevel gear at lower end of vertical drive shaft in foreground turned bevel gear of top roll when the vertical drive shaft was in place in the brass-bearing socket in the middle ground of the photograph. The bolts above the top roll and at the side of the two bottom rolls adjusted the pressure and position of the rolls' brass bearings. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

Genetics Home Reference: DOLK-congenital disorder of glycosylation

MedlinePlus

... called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation changes proteins in ways that ... to dolichol phosphate in order to build the oligosaccharide chain. Once the chain is formed, dolichol phosphate ...

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

PubMed

Marx, Dagen C; Fleming, Karen G

2017-08-08

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

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

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

2016-01-01

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

Phase separation of comb polymer nanocomposite melts.

PubMed

Xu, Qinzhi; Feng, Yancong; Chen, Lan

2016-02-07

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

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

PubMed

Lietzow, Michael A; Hubbell, Wayne L

2004-03-23

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

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

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Kurosu, Hiromichi; Shoji, Akira

2010-04-01

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

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

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

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

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

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

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.

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.

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

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 incorporation of urea groups in the side chains induces the polymer chains to pack more orderly and form large domains because of the additional H-bonding among urea groups. Accordingly, thin film mobilities of the conjugated D-A polymers with side chains entailing urea groups are largely boosted in comparison with those of polymers of the same backbones with either branching alkyl chains or branching/linear alkyl chains. (iv) The torsions of branching alkyl chains in conjugated D-A polymers can be inhibited to some extent upon incorporation of tiny amount of NMe 4 I in the thin film. As a result, the polymer thin films with NMe 4 I exhibit improved crystallinity, and charge mobilities can be boosted by more than 20 times. (v) Side chains with functional groups in the conjugated polymers can endow the thin film field-effect transistors (FETs) with sensing functionality. FETs with the conjugated polymer with -COOH groups in the side chains show sensitive, selective, and fast responses toward ammonia and amines, while FETs with the ultrathin films of the polymer containing tetra(ethylene glycol) (TEEG) in the side chains can sense alcohol vapors (in particular ethanol vapor) sensitively and selectively with fast response.

U.S.-Mexico Economic Relations: Trends, Issues, and Implications

DTIC Science & Technology

2010-03-31

resolved a long-standing trade dispute in 2006 involving sugar and high fructose corn syrup . Mexico argued that the sugar side letter negotiated under...Research Service 23 complained that imports of high fructose corn syrup (HFCS) sweeteners from the United States constituted dumping, and it imposed anti...made with corn syrup sweeteners to aid the ailing domestic cane sugar industry, and subsequently extended the tax annually despite U.S. objections

Comparative metabolite profiling of Solanum tuberosum against six wild Solanum species with Colorado potato beetle resistance.

PubMed

Tai, Helen H; Worrall, Kraig; Pelletier, Yvan; De Koeyer, David; Calhoun, Larry A

2014-09-10

The Colorado potato beetle Leptinotarsa decemlineata (Say) (CPB) is a coleopteran herbivore that feeds on the foliage on Solanum species, in particular, potato. Six resistant wild Solanum species were identified, and two of these species had low levels of glycoalkaloids. Comparative analysis of the untargeted metabolite profiles of the foliage using UPLC-qTOF-MS was done to find metabolites shared between the wild species but not with Solanum tuberosum (L.) to identify resistance-related metabolites. It was found that only S. tuberosum produced the triose glycoalkaloids solanine and chaconine. Instead, the six wild species produced glycoalkaloids that shared in common tetrose sugar side chains. Additionally, there were non-glycoalkaloid metabolites associated with resistance including hydroxycoumarin and a phenylpropanoid, which were produced in all wild species but not in S. tuberosum.

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

DOE PAGES

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

2017-04-07

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

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

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

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

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

34. RW Meyer Sugar Mill: 18761889. Threeroll sugar mill, oneton ...

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

34. RW Meyer Sugar Mill: 1876-1889. Three-roll sugar mill, one-ton daily processing capacity. Manufactured by Edwin Maw, Liverpool, England, ca. 1855-1870. View: Side view of mill. Vertical drive shaft lying on ground in foreground. When drive-shaft was in upright position its bevel gear was meshed with the bevel gear of the top roll, transmitting the animals'circular motion around the drive shaft to the horizontal rolls. The foundation is of portland cement. The heavy timber mill bed, between the mill and the portland cement foundation has rolled away. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

A protein-dependent side-chain rotamer library.

PubMed

Bhuyan, Md Shariful Islam; Gao, Xin

2011-12-14

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

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

PubMed

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

2017-04-11

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

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

PubMed

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

2004-07-01

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

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

PubMed

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

2015-03-01

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

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

PubMed

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

2017-11-24

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

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

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

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

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

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

DOE PAGES

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

2017-02-24

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

Relationship between ion pair geometries and electrostatic strengths in proteins.

PubMed Central

Kumar, Sandeep; Nussinov, Ruth

2002-01-01

The electrostatic free energy contribution of an ion pair in a protein depends on two factors, geometrical orientation of the side-chain charged groups with respect to each other and the structural context of the ion pair in the protein. Conformers in NMR ensembles enable studies of the relationship between geometry and electrostatic strengths of ion pairs, because the protein structural contexts are highly similar across different conformers. We have studied this relationship using a dataset of 22 unique ion pairs in 14 NMR conformer ensembles for 11 nonhomologous proteins. In different NMR conformers, the ion pairs are classified as salt bridges, nitrogen-oxygen (N-O) bridges and longer-range ion pairs on the basis of geometrical criteria. In salt bridges, centroids of the side-chain charged groups and at least a pair of side-chain nitrogen and oxygen atoms of the ion-pairing residues are within a 4 A distance. In N-O bridges, at least a pair of the side-chain nitrogen and oxygen atoms of the ion-pairing residues are within 4 A distance, but the distance between the side-chain charged group centroids is greater than 4 A. In the longer-range ion pairs, the side-chain charged group centroids as well as the side-chain nitrogen and oxygen atoms are more than 4 A apart. Continuum electrostatic calculations indicate that most of the ion pairs have stabilizing electrostatic contributions when their side-chain charged group centroids are within 5 A distance. Hence, most (approximately 92%) of the salt bridges and a majority (68%) of the N-O bridges are stabilizing. Most (approximately 89%) of the destabilizing ion pairs are the longer-range ion pairs. In the NMR conformer ensembles, the electrostatic interaction between side-chain charged groups of the ion-pairing residues is the strongest for salt bridges, considerably weaker for N-O bridges, and the weakest for longer-range ion pairs. These results suggest empirical rules for stabilizing electrostatic interactions in proteins. PMID:12202384

A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

PubMed Central

Gysi, Stephan; Rhiner, Christa; Flibotte, Stephane; Moerman, Donald G.; Hengartner, Michael O.

2013-01-01

Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons. PMID:24066155

16. RW Meyer Sugar Mill: 18761889. Boiling House Interior, 1878. ...

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

16. RW Meyer Sugar Mill: 1876-1889. Boiling House Interior, 1878. View: Looking from west to east through boiling house. The sorghum pan is on the right. The beams; joists, and trusses are of northwest pine; side boards are of redwood. A foundation line of a loading dock and smokestack are in the foreground. Both end walls have deteriorated completely. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

Ionizable side chains at catalytic active sites of enzymes.

PubMed

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

2012-05-01

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

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

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

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

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

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.

Osmotic stress is accompanied by protein glycation in Arabidopsis thaliana.

PubMed

Paudel, Gagan; Bilova, Tatiana; Schmidt, Rico; Greifenhagen, Uta; Berger, Robert; Tarakhovskaya, Elena; Stöckhardt, Stefanie; Balcke, Gerd Ulrich; Humbeck, Klaus; Brandt, Wolfgang; Sinz, Andrea; Vogt, Thomas; Birkemeyer, Claudia; Wessjohann, Ludger; Frolov, Andrej

2016-12-01

Among the environmental alterations accompanying oncoming climate changes, drought is the most important factor influencing crop plant productivity. In plants, water deficit ultimately results in the development of oxidative stress and accumulation of osmolytes (e.g. amino acids and carbohydrates) in all tissues. Up-regulation of sugar biosynthesis in parallel to the increasing overproduction of reactive oxygen species (ROS) might enhance protein glycation, i.e. interaction of carbonyl compounds, reducing sugars and α-dicarbonyls with lysyl and arginyl side-chains yielding early (Amadori and Heyns compounds) and advanced glycation end-products (AGEs). Although the constitutive plant protein glycation patterns were characterized recently, the effects of environmental stress on AGE formation are unknown so far. To fill this gap, we present here a comprehensive in-depth study of the changes in Arabidopsis thaliana advanced glycated proteome related to osmotic stress. A 3 d application of osmotic stress revealed 31 stress-specifically and 12 differentially AGE-modified proteins, representing altogether 56 advanced glycation sites. Based on proteomic and metabolomic results, in combination with biochemical, enzymatic and gene expression analysis, we propose monosaccharide autoxidation as the main stress-related glycation mechanism, and glyoxal as the major glycation agent in plants subjected to drought. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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

Characterization and bioactivities of a novel polysaccharide obtained from Gracilariopsis lemaneiformis.

PubMed

Shi, Chen-Shan; Sang, Ya-Xin; Sun, Gui-Qing; Li, Tian-Ye; Gong, Zheng-Si; Wang, Xiang-Hong

2017-01-01

Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by β-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.

Structural characterization of anti-complementary polysaccharides from the leaves of Artemisia princeps.

PubMed

Yamada, H; Otsuka, Y; Omura, S

1986-08-01

Structural characterizations of the anti-complementary acidic heteroglycans, AAF IIb-2 and IIb-3, obtained from the leaves of Artemisia princeps pamp have been studied. AAF IIb-2 consists of rhamnose, xylose, arabinose, galactose, glucose and uronic acids (glucuronic acid and galacturonic acid) in the molar ratio of 7.6:7.6:13.0:10.9:3.0:57.9, and AAF IIb-3 consists of the same sugars in the ratio of 3.9:2.6:24.7:19.7:2.6:46.5. Methylation analysis including carboxyl-reduction and also selective enzymolysis using EXO-alpha- L-arabinofuranosidase suggested that AAF IIb-3 has a main chain consisting of (1-->4)-linked galacturonic acid and (1-->2)-linked rhamnose mostly substituted at the O-4 position. AAF IIb-3 also contained arabino-3,6-galactan moiety and most of the arabinose was present as an alpha- L-furanosyl residue in the non-reducing terminals and highly branched side chains which mostly attached to the O-3 position of (1-->6)-linked galactopyranosyl residue. The basic structure of AAF IIb-2 is similar to that of AAF IIb-3, but IIb-3 has a higher arabinogalactan content than IIb-2.

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.

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.

Improved packing of protein side chains with parallel ant colonies.

PubMed

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

2014-01-01

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

Glycation of myofibrillar proteins and ATPase activity after incubation with eleven sugars.

PubMed

Syrový, I

1994-01-01

Rat skeletal muscle myofibrils were incubated in the presence of D-glucose, D-fructose, D-galactose, D-ribose, D-tagatose, D-arabinose, D-xylose, D-mannose, L-sorbose, L-rhamnose or DL-glyceraldehyde and myofibrillar ATPase activity as well as the extent of glycation was measured. The attachment of sugars to proteins during glycation was generally dependent on the percentage of a given sugar present in the open-chain form. Glycation resulted in the decrease of myofibrillar ATPase activity. This decrease was low after incubation of myofibrillar proteins with slowly glycating sugars (e.g. glucose) and high with fast glycating sugars (e.g. ribose or glyceraldehyde). ATPase activity was less reduced in the presence of beta-mercaptoethanol.

Inverse hexagonal and cubic micellar lyotropic liquid crystalline phase behaviour of novel double chain sugar-based amphiphiles.

PubMed

Feast, George C; Lepitre, Thomas; Tran, Nhiem; Conn, Charlotte E; Hutt, Oliver E; Mulet, Xavier; Drummond, Calum J; Savage, G Paul

2017-03-01

The lyotropic phase behaviour of a library of sugar-based amphiphiles was investigated using high-throughput small-angle X-ray scattering (SAXS). Double unsaturated-chain monosaccharide amphiphiles formed inverse hexagonal and cubic micellar (Fd3m) lyotropic phases under excess water conditions. A galactose-oleyl amphiphile from the library was subsequently formulated into hexosome nanoparticles, which have potential uses as drug delivery vehicles. The nanoparticles were shown to be stable at elevated temperatures and non-cytotoxic up to at least 200μgmL -1 . Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Targeting of asialofetuin sugar chain-bearing liposomes to liver lysosomes.

PubMed

Banno, Y; Ohki, K; Nozawa, Y

1983-10-01

Specific direction of liposomes bearing an asialofetuin sugar chain (AFSC) to liver parenchymal cells was examined both in vivo and in vitro. The AFSC-bearing liposomes were preferentially recovered in the liver within several minutes after an intravenous injection into mice and were found to be predominantly localized in mitochondrial-lysosomal fraction. The massive distribution of the AFSC-liposomes in this fraction was also confirmed by using a lysosomal protease inhibitor, E-64-d. In isolated rat hepatocytes, the uptake of AFSC-liposomes was increased 2-3-fold as compared with the control liposomes without AFSC. Thus liposomes bearing AFSC would be useful to target enzymes to liver lysosomes.

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

Conditional solvation thermodynamics of isoleucine in model peptides and the limitations of the group-transfer model.

PubMed

Tomar, Dheeraj S; Weber, Valéry; Pettitt, B Montgomery; Asthagiri, D

2014-04-17

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

Human tolerance to a single, high dose of D-tagatose.

PubMed

Buemann, B; Toubro, S; Raben, A; Astrup, A

1999-04-01

The addition of 29 g D-tagatose added as a sweetener to a continental breakfast was tested for the appearance of gastrointestinal side effects in a double-blind randomized cross-over study with 29 g sucrose as a control treatment. The subjects reported the side effects during 72 h following the test meal on a questionnaire grading the symptoms on a five-level scale ranging from "none" to "very strong." Although "rumbling in the stomach," "distention," "nausea," "rumbling in the gut," "flatulence, " and "diarrhea" scored significantly higher with D-tagatose, the sugar otherwise was well tolerated in most of the subjects. Two cases of vomiting after D-tagatose were recorded but in one of the cases its relation to the D-tagatose intake was questionable. Only the "distention" score remained higher with D-tagatose for more than 24 h. Nausea, vomiting, and perceived distension may be due to an osmotic effect in the small intestine of unabsorbed D-tagatose. The increased flatus is caused by D-tagatose being fermented in the large intestine. Diarrhea may be explained by osmotic effects in the colon from nondegraded D-tagatose or nonabsorbed short-chain fatty acids produced by the increased fermentation. Copyright 1999 Academic Press.

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.

Effects of antibiotics on human microbiota and subsequent disease.

PubMed

Keeney, Kristie M; Yurist-Doutsch, Sophie; Arrieta, Marie-Claire; Finlay, B Brett

2014-01-01

Although antibiotics have significantly improved human health and life expectancy, their disruption of the existing microbiota has been linked to significant side effects such as antibiotic-associated diarrhea, pseudomembranous colitis, and increased susceptibility to subsequent disease. By using antibiotics to break colonization resistance against Clostridium, Salmonella, and Citrobacter species, researchers are now exploring mechanisms for microbiota-mediated modulation against pathogenic infection, revealing potential roles for different phyla and family members as well as microbiota-liberated sugars, hormones, and short-chain fatty acids in regulating pathogenicity. Furthermore, connections are now being made between microbiota dysbiosis and a variety of different diseases such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, atopy, and obesity. Future advances in the rapidly developing field of microbial bioinformatics will enable researchers to further characterize the mechanisms of microbiota modulation of disease and potentially identify novel therapeutics against disease.

Cytotoxicity of natural ginseng glycosides and semisynthetic analogues.

PubMed

Atopkina, L N; Malinovskaya, G V; Elyakov, G B; Uvarova, N I; Woerdenbag, H J; Koulman, A; Pras, N; Potier, P

1999-02-01

The cytotoxicity of natural glycosides from Ginseng, semisynthetic analogues and related triterpenes of the dammarane series, isolated from the leaves of the Far-East species of the genus Betula was studied in order to elucidate structure-activity relationships. Some of the compounds studied were active against the human lung carcinoma GLC4 and adenocarcinoma COLO 320 cell lines. The natural glycosides displayed the lowest cytotoxicity. The triterpenes of the dammarane series used as starting aglycones for semisynthetic derivatives were moderately cytotoxic. The dammarane triterpenes possessing keto groups and their semisynthetic glucosides were the most active compounds tested. Cytotoxic effects of the dammarane glucosides were inversely proportional both to the number of sugars attached to the aglycones and to the number of hydroxy groups of the aglycones. The type of side chain and the configuration of the hydroxy group at C-3 in aglycones did not have a significant influence on the cytotoxicity.

6. Looking west from the roadway on the bridge, this ...

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

6. Looking west from the roadway on the bridge, this view portrays the more densely wooded terrain which is part of the environment surrounding Sugar Creek on the upstream side of the bridge - Vigo County Bridge No. 139, Spanning Sugar Creek at Seventy-fourth Place, Terre Haute, Vigo County, IN

Sugar reduction without compromising sensory perception. An impossible dream?

PubMed

Hutchings, Scott C; Low, Julia Y Q; Keast, Russell S J

2018-03-21

Sugar reduction is a major technical challenge for the food industry to address in response to public health concerns regarding the amount of added sugars in foods. This paper reviews sweet taste perception, sensory methods to evaluate sugar reduction and the merits of different techniques available to reduce sugar content. The use of sugar substitutes (non-nutritive sweeteners, sugar alcohols, and fibres) can achieve the greatest magnitude of sugar and energy reduction, however bitter side tastes and varying temporal sweet profiles are common issues. The use of multisensory integration principles (particularly aroma) can be an effective approach to reduce sugar content, however the magnitude of sugar reduction is small. Innovation in food structure (modifying the sucrose distribution, serum release and fracture mechanics) offers a new way to reduce sugar without significant changes in food composition, however may be difficult to implement in food produced on a large scale. Gradual sugar reduction presents difficulties for food companies from a sales perspective if acceptability is compromised. Ultimately, a holistic approach where food manufacturers integrate a range of these techniques is likely to provide the best progress. However, substantial reduction of sugar in processed foods without compromising sensory properties may be an impossible dream.

Direct evidence for the ring opening of monosaccharide anions in the gas phase: photodissociation of aldohexoses and aldohexoses derived from disaccharides using variable-wavelength infrared irradiation in the carbonyl stretch region.

PubMed

Brown, Darin J; Stefan, Sarah E; Berden, Giel; Steill, Jeffrey D; Oomens, Jos; Eyler, John R; Bendiak, Brad

2011-11-08

All eight D-aldohexoses and aldohexoses derived from the non-reducing end of disaccharides were investigated by variable-wavelength infrared multiple-photon dissociation (IRMPD) as anions in the negative-ion mode. Spectroscopic evidence supports the existence of a relatively abundant open-chain configuration of the anions in the gas phase, based on the observation of a significant carbonyl absorption band near 1710 cm(-1). The abundance of the open-chain configuration of the aldohexose anions was approximately 1000-fold or greater than that of the neutral sugars in aqueous solution. This provides an explanation as to why it has not been possible to discriminate the anomeric configuration of aldohexose anions in the gas phase when derived from the non-reducing sugar of a disaccharide. Evidence from photodissociation spectra also indicates that the different aldohexoses yield product ions with maximal abundances at different wavelengths, and that the carbonyl stretch region is useful for differentiation of sugar stereochemistries. Quantum-chemical calculations indicate relatively low energy barriers to intramolecular proton transfer between hydroxyl groups and adjacent alkoxy sites located on open-chain sugar anions, suggesting that an ensemble of alkoxy charge locations contributes to their observed photodissociation spectra. Ring opening of monosaccharide anions and interconversion among configurations is an inherent property of the ions themselves and occurs in vacuo independent of solvent participation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Postprandial glycaemic and insulinaemic responses in adults after consumption of dairy desserts and pound cakes containing short-chain fructo-oligosaccharides used to replace sugars.

PubMed

Lecerf, J M; Clerc, E; Jaruga, A; Wagner, A; Respondek, F

2015-01-01

The present studies aimed to evaluate the glycaemic and insulinaemic responses, in healthy adults, to short-chain fructo-oligosaccharides (scFOS) from sucrose used to replace sugars in foods. Two study populations aged 18-50 years were recruited and they consumed dairy desserts or pound cakes containing either standard sugar content or scFOS to replace 30 % of the sugar content. For each study, the two products were tested once under a double-blind and cross-over design with at least 7 d between the two tests. Glucose and insulin were measured using standard methods in blood samples collected with a venous catheter for 120 min during a kinetic test. For the dairy desserts, replacing 30 % of the sugars with scFOS significantly reduced postprandial glycaemic (AUC0-120 min; P = 0·020) and insulinaemic (AUC0-120 min; P = 0·003) responses. For the pound cakes, the glycaemic response was not altered (AUC0-120 min; P =  0·322) while the insulinaemic response tended to be lower (AUC0-120 min; P = 0·067). This study showed that scFOS can be used to replace sugars with the benefit of lowering the postprandial glycaemic response without increasing the insulinaemic response. The effect might be modulated by other parameters (e.g. fat content) of the food matrices.

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.

Laser amplifier chain

DOEpatents

Hackel, Richard P.

1992-01-01

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

Linear rheology and structure of molecular bottlebrushes with short side chains

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

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

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

Selenium and arsenic in biology: their chemical forms and biological functions.

PubMed

Shibata, Y; Morita, M; Fuwa, K

1992-01-01

Based on the recent development of analytical methods, sensitive systems for the analysis and speciation of selenium and arsenic have been established. A palladium addition technique was developed for the accurate determination of selenium in biological samples using graphite furnace atomic absorption analysis. For the speciation of the elements, combined methods of HPLC either with ICP-AES or with ICP-MS were found to work well. These systems were applied to the elucidation of the chemical form of the elements in natural samples. Some chemical properties of the selenium-mercury complex in dolphin liver were elucidated: i.e., it was a cationic, water-soluble, low molecular weight compound containing selenium and mercury in a 1:1 molar ratio, and was shown to be different from a known selenium-mercury complex, bis(methylmercuric)selenide. The major selenium compound excreted in human urine was revealed to be other than any of those previously identified (TMSe, selenate, and selenite). TMSe, a suspected major metabolite in urine, was found, if at all, in low levels. The major water-soluble, and lipid-soluble arsenic compounds in a brown seaweed, U. pinnatifida (WAKAME), were rigorously identified, and the results were compared with other data on marine algae and animals. The major organic arsenic compounds (termed "arseno-sugars") in marine algae commonly contain 5-deoxy-5-dimethylarsinyl-ribofuranoside moiety. There are various kinds of arseno-sugar derivatives containing different side-chains attached to the anomeric position of the sugar, and the distribution of each arsenic species seems to be related to algal species. The arseno-sugar (A-XI) is present in every alga so far examined, is metabolized to lipids, and possibly may play some specific role in the algal cells. On the other hand, the major arsenic compound in fish, crustacea and molluscs has been identified as arsenobetaine, which is an arseno-analog of glycinebetaine, a very common osmo-regulator in living organisms. Arsenobetaine is not detected in marine algae while arseno-sugars are not present in marine animals except for some molluscs which contain both compounds in considerable amounts. Arsenobetaine is present in the urine of human beings who have eaten foods derived from marine animals.

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).

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.

Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

PubMed Central

Hyslop, Newton E.; Milligan, Richard J.

1974-01-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed Central

2015-01-01

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

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

NASA Astrophysics Data System (ADS)

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

1989-06-01

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

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

PubMed

Tobias, Fernando; Keiderling, Timothy A

2016-05-10

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

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

PubMed

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

2013-04-02

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

Energy balances in sugar cane, coffee and natural vegetation in the northeastern side of the São Paulo state, Brazil

NASA Astrophysics Data System (ADS)

de C. Teixeira, Antônio H.; Leivas, Janice F.; Ronquim, Carlos C.; Bayma-Silva, Gustavo; de C. Victoria, Daniel

2016-10-01

Under land and climate change scenarios, agriculture has experienced water competitions among other sectors in the São Paulo state, Brazil. On the one hand, in several occasions, in the northeastern side of this state, nowadays sugar-cane is expanding, while coffee plantations are losing space. On the other hand, both crops have replaced the natural vegetation composed by Savannah and Atlantic Coastal Forest species. Under this dynamic situation, geosciences are valuable tools for evaluating the large-scale energy and mass exchanges between these different agro-ecosystems and the lower atmosphere. For quantification of the energy balance components in these mixed agro-ecosystems, the bands 1 and 2 from the MODIS product MOD13Q1 were used throughout SAFER (Surface Algorithm for Evapotranspiration Retrieving) algorithm, which was applied together with a net of 12 automatic weather stations, during the year 2015 in the main sugar cane and coffee growing regions, located at the northeastern side of the state. The fraction of the global solar radiation (RG) transformed into net radiation (Rn) was 52% for sugar cane and 53% for both, coffee and natural vegetation. The respective annual fractions of Rn used as λE were 0.68, 0.87 and 0.77, while for the sensible heat (H) fluxes they were 0.27, 0.07 and 0.16. From April to July, heat advection raised λE values above Rn promoting negative H, however these effects were much and less strong in coffee and sugar cane crops, respectively. The smallest daily Rn fraction for all agro-ecosystems was for the soil heat flux (G), with averages of 5%, 6% and 7% in sugar cane, coffee and natural vegetation. From the energy balance analyses, we could conclude that, sugar-cane crop presented lower annual water consumption than that for coffee crop, what can be seen as an advantage in situations of water scarcity. However, the replacement of natural vegetation by sugar cane can contribute for warming the environment, while when this occur with coffee crop there was noticed cooling conditions. The large scale modeling satisfactory results confirm the suitability of using MODIS products together with weather stations to study the energy balance components in mixed agro-ecosystems under land-use and climate change conditions.

Laser amplifier chain

DOEpatents

Hackel, R.P.

1992-10-20

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

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

PubMed

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

2015-08-15

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

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

PubMed Central

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

1991-01-01

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

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

PubMed

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

2004-09-01

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

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

NASA Astrophysics Data System (ADS)

Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

2017-09-01

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

Improved packing of protein side chains with parallel ant colonies

PubMed Central

2014-01-01

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

Detection of glycosylation abnormality in rheumatoid IgG using N-acetylglucosamine-specific Psathyrella velutina lectin.

PubMed

Tsuchiya, N; Endo, T; Matsuta, K; Yoshinoya, S; Takeuchi, F; Nagano, Y; Shiota, M; Furukawa, K; Kochibe, N; Ito, K

1993-07-15

Although the galactose deficiency in the Asn297-linked sugar chains of serum IgG from patients with rheumatoid arthritis (RA) has been established, structural analysis of sugar chains has not been readily available. Psathyrella velutina lectin (PVL) preferentially interacts with the N-acetylglucosamine beta 1-->2Man group, exposed at the termini of sugar chains in agalacto IgG. Biotinylated PVL reacted strongly in Western blotting with H chains of IgG derived from patients with RA. An ELISA-based assay for the detection of agalacto IgG was developed using recombinant protein G and biotinylated PVL in combination, and the screening of patients' sera was performed. PVL binding of serum IgG significantly correlated with percentage of galactose-deficient IgG determined by the structural analysis. Age-related slight increase in PVL binding was observed among normal controls. Patients with RA showed significantly higher PVL binding (37.90 +/- 42.25 U/ml, n = 93) as compared with normal controls (5.75 +/- 2.92 U/ml, n = 112) (p = 0.0001). Patients with SLE showed lower but still significant PVL binding (17.86 +/- 5.18 U/ml, n = 10, p = 0.0001). PVL binding correlated with C-reactive protein level in serial analysis of individual RA patients, and was significantly higher in the synovial fluid compared with paired serum samples. PVL binding assay may provide an ideal tool for the simple and sensitive detection of agalacto IgG.

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.

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.

The Conversion of Starch and Sugars into Branched C10 and C11 Hydrocarbons.

PubMed

Sutton, Andrew D; Kim, Jin K; Wu, Ruilian; Hoyt, Caroline B; Kimball, David B; Silks, Louis A; Gordon, John C

2016-09-08

Oligosaccharides, such as starch, cellulose, and hemicelluloses, are abundant and easily obtainable bio-derived materials that can potentially be used as precursors for fuels and chemical feedstocks. To access the pertinent molecular building blocks (i.e., 5- or 6-carbon containing sugar units) located within these biopolymers and transform them into useful fuel precursors, oligosaccharide depolymerization followed by chain extension is required. This chain extension can readily be performed via a Garcia-Gonzalez-like approach using β-diketones under mild conditions to provide fuel precursors containing an increased carbon atom content that meets fuel requirements. In a subsequent step, ring opening and hydrodeoxygenation chemistry of these species allows for the preparation of branched alkanes under relatively mild conditions. This approach can be applied to monomeric sugars (glucose and xylose), oligosaccharides (starch), and potentially to hydrolyzed dedicated energy crops to allow the conversion of real biomass into fuel type molecules. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acylsugar Acylhydrolases: Carboxylesterase-Catalyzed Hydrolysis of Acylsugars in Tomato Trichomes1[OPEN

PubMed Central

Gilgallon, Karin; Ghosh, Banibrata

2016-01-01

Glandular trichomes of cultivated tomato (Solanum lycopersicum) and many other species throughout the Solanaceae produce and secrete mixtures of sugar esters (acylsugars) on the plant aerial surfaces. In wild and cultivated tomato, these metabolites consist of a sugar backbone, typically glucose or sucrose, and two to five acyl chains esterified to various positions on the sugar core. The aliphatic acyl chains vary in length and branching and are transferred to the sugar by a series of reactions catalyzed by acylsugar acyltransferases. A phenotypic screen of a set of S. lycopersicum M82 × Solanum pennellii LA0716 introgression lines identified a dominant genetic locus on chromosome 5 from the wild relative that affected total acylsugar levels. Genetic mapping revealed that the reduction in acylsugar levels was consistent with the presence and increased expression of two S. pennellii genes (Sopen05g030120 and Sopen05g030130) encoding putative carboxylesterase enzymes of the α/β-hydrolase superfamily. These two enzymes, named ACYLSUGAR ACYLHYDROLASE1 (ASH1) and ASH2, were shown to remove acyl chains from specific positions of certain types of acylsugars in vitro. A survey of related genes in M82 and LA0716 identified another trichome-expressed ASH gene on chromosome 9 (M82, Solyc09g075710; LA0716, Sopen09g030520) encoding a protein with similar activity. Characterization of the in vitro activities of the SpASH enzymes showed reduced activities with acylsugars produced by LA0716, presumably contributing to the high-level production of acylsugars in the presence of highly expressed SpASH genes. PMID:26811191

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

PubMed

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

2005-11-18

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

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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

PubMed

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

2015-04-01

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

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

PubMed

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

2011-05-19

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

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

PubMed Central

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

2012-01-01

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

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

DTIC Science & Technology

1986-10-01

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

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

PubMed

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

2010-07-07

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

How accurately do force fields represent protein side chain ensembles?

PubMed

Petrović, Dušan; Wang, Xue; Strodel, Birgit

2018-05-23

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

23. RW Meyer Sugar Mill: 18761889. Boiling House Interior, 1878. ...

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

23. RW Meyer Sugar Mill: 1876-1889. Boiling House Interior, 1878. View: North Wall of boiling house. In the original structure the three windows on the right admitted light and air from the outside. A shed occupied the left side of the wall outside (hence no windows). in 1881 the construction of the cooling shed closed in the right three windows. The sorghum is in the foreground. The centrifugals are in the left rear. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

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

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

PubMed Central

INOUE, Masayuki

2014-01-01

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

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

PubMed

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

2017-10-04

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

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.

A Basal Stem Canker of Sugar Maple

Treesearch

Kenneth J. Jr. Kessler

1969-01-01

A basal stem canker of sugar maple is common on trees in lightly stocked stands and on trees on the north side of roads and other clearings in the Lake States. The cankers are usually elongate, usually encompass about one-fourth of the stem circumference, and face the south. Most cankers originate following logging of old-growth stands on stems that had been present...

Dissociation reactions of protonated anthracycline antibiotics following electrospray ionization-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Sleno, Lekha; Campagna-Slater, Valerie; Volmer, Dietrich A.

2006-09-01

Fragmentation pathways of doxorubicin, a common cancer therapy agent, and three closely related analogs (epirubicin, daunorubicin, idarubicin) were compared using electrospray ionization with tandem mass spectrometry. This class of antibiotics with anti-tumour activity has important structural features, with a tetracyclic aromatic, polyketide portion, which is glycosylated with an amino sugar in order to exhibit its biological activity. Collision-induced dissociation spectra revealed very similar product ions for each analog, however, important differences were seen in the relative abundances and the ease at which certain fragments were formed. Fragment ions observed included those from cleavage of the glycosidic bond, loss of the side chain from the aglycone moiety, water losses and loss of a methyl radical. Following cleavage of the glycosidic bond, the charge can either reside on the aglycone portion or the sugar moiety, and each of these primary fragments undergoes several secondary dissociation pathways, depending on the collision energy. By ramping the collision voltage, we were able to correlate the changes in fragmentation behavior with small alterations in the structure of the precursor ion. The detailed study of the fragmentation behavior of doxorubicin was supported by accurate mass measurements, using an electrospray-time of flight instrument, as well as MS3 data from a quadrupole-linear ion trap mass spectrometer. Computational studies were also performed to help explain the role of certain functional groups in the fragmentation reactions.

Genomics Review of Holocellulose Deconstruction by Aspergilli

PubMed Central

Segato, Fernando; Damásio, André R. L.; de Lucas, Rosymar C.; Squina, Fabio M.

2014-01-01

SUMMARY Biomass is constructed of dense recalcitrant polymeric materials: proteins, lignin, and holocellulose, a fraction constituting fibrous cellulose wrapped in hemicellulose-pectin. Bacteria and fungi are abundant in soil and forest floors, actively recycling biomass mainly by extracting sugars from holocellulose degradation. Here we review the genome-wide contents of seven Aspergillus species and unravel hundreds of gene models encoding holocellulose-degrading enzymes. Numerous apparent gene duplications followed functional evolution, grouping similar genes into smaller coherent functional families according to specialized structural features, domain organization, biochemical activity, and genus genome distribution. Aspergilli contain about 37 cellulase gene models, clustered in two mechanistic categories: 27 hydrolyze and 10 oxidize glycosidic bonds. Within the oxidative enzymes, we found two cellobiose dehydrogenases that produce oxygen radicals utilized by eight lytic polysaccharide monooxygenases that oxidize glycosidic linkages, breaking crystalline cellulose chains and making them accessible to hydrolytic enzymes. Among the hydrolases, six cellobiohydrolases with a tunnel-like structural fold embrace single crystalline cellulose chains and cooperate at nonreducing or reducing end termini, splitting off cellobiose. Five endoglucanases group into four structural families and interact randomly and internally with cellulose through an open cleft catalytic domain, and finally, seven extracellular β-glucosidases cleave cellobiose and related oligomers into glucose. Aspergilli contain, on average, 30 hemicellulase and 7 accessory gene models, distributed among 9 distinct functional categories: the backbone-attacking enzymes xylanase, mannosidase, arabinase, and xyloglucanase, the short-side-chain-removing enzymes xylan α-1,2-glucuronidase, arabinofuranosidase, and xylosidase, and the accessory enzymes acetyl xylan and feruloyl esterases. PMID:25428936

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

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

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

PubMed

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

2015-12-10

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

Structural analysis of a highly glycosylated and unliganded gp120-based antigen using mass spectrometry†

PubMed Central

Wang, Liwen; Qin, Yali; Ilchenko, Serguei; Bohon, Jen; Shi, Wuxian; Cho, Michael W.; Takamoto, Keiji; Chance, Mark R.

2010-01-01

Structural characterization of the HIV envelope protein gp120 is very important to provide an understanding of the protein's immunogenicity and it's binding to cell receptors. So far, crystallographic structure determination of gp120 with an intact V3 loop (in the absence of CD4 co-receptor or antibody) has not been achieved. The third variable region (V3) of the gp120 is immunodominant and contains glycosylation signatures that are essential for co-receptor binding and viral entry to T-cells. In this study, we characterized the structure of the outer domain of gp120 with an intact V3 loop (gp120-OD8) purified from Drosophila S2 cells utilizing mass spectrometry-based approaches. We mapped the glycosylation sites and calculated glycosylation occupancy of gp120-OD8; eleven sites from fifteen glycosylation motifs were determined as having high mannose or hybrid glycosylation structures. The specific glycan moieties of nine glycosylation sites from eight unique glycopeptides were determined by a combination of ECD and CID MS approaches. Hydroxyl radical-mediated protein footprinting coupled with mass spectrometry analysis was employed to provide detailed information on protein structure of gp120-OD8 by directly identifying accessible and hydroxyl radical-reactive side chain residues. Comparison of gp120-OD8 experimental footprinting data with a homology model derived from the ligated CD4/ gp120-OD8 crystal structure revealed a flexible V3 loop structure where the V3 tip may provide contacts with the rest of the protein while residues in the V3 base remain solvent accessible. In addition, the data illustrate interactions between specific sugar moieties and amino acid side chains potentially important to the gp120-OD8 structure. PMID:20825246

Crystal Structure of the Catalytic Domain of Drosophila [beta]1,4-Galactosyltransferase-7

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

Ramakrishnan, Boopathy; Qasba, Pradman K.

2010-11-03

The {beta}1,4-galactosyltransferase-7 ({beta}4Gal-T7) enzyme, one of seven members of the {beta}4Gal-T family, transfers in the presence of manganese Gal from UDP-Gal to an acceptor sugar (xylose) that is attached to a side chain hydroxyl group of Ser/Thr residues of proteoglycan proteins. It exhibits the least protein sequence similarity with the other family members, including the well studied family member {beta}4Gal-T1, which, in the presence of manganese, transfers Gal from UDP-Gal to GlcNAc. We report here the crystal structure of the catalytic domain of {beta}4Gal-T7 from Drosophila in the presence of manganese and UDP at 1.81 {angstrom} resolution. In the crystalmore » structure, a new manganese ion-binding motif (HXH) has been observed. Superposition of the crystal structures of {beta}4Gal-T7 and {beta}4Gal-T1 shows that the catalytic pocket and the substrate-binding sites in these proteins are similar. Compared with GlcNAc, xylose has a hydroxyl group (instead of an N-acetyl group) at C2 and lacks the CH{sub 2}OH group at C5; thus, these protein structures show significant differences in their acceptor-binding site. Modeling of xylose in the acceptor-binding site of the {beta}4Gal-T7 crystal structure shows that the aromatic side chain of Tyr{sup 177} interacts strongly with the C5 atom of xylose, causing steric hindrance to any additional group at C5. Because Drosophila Cd7 has a 73% protein sequence similarity to human Cd7, the present crystal structure offers a structure-based explanation for the mutations in human Cd7 that have been linked to Ehlers-Danlos syndrome.« less

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.

Distribution Analysis of Anthocyanins, Sugars, and Organic Acids in Strawberry Fruits Using Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry.

PubMed

Enomoto, Hirofumi; Sato, Kei; Miyamoto, Koji; Ohtsuka, Akira; Yamane, Hisakazu

2018-05-16

Anthocyanins, sugars, and organic acids contribute to the appearance, health benefits, and taste of strawberries. However, their spatial distribution in the ripe fruit has been fully unrevealed. Therefore, we performed matrix-assisted laser desorption/ionization, MALDI-IMS, analysis to investigate their spatial distribution in ripe strawberries. The detection sensitivity was improved by using the TM-Sprayer for matrix application. In the receptacle, pelargonidins were distributed in the skin, cortical, and pith tissues, whereas cyanidins and delphinidins were slightly localized in the skin. In the achene, mainly cyanidins were localized in the outside of the skin. Citric acid was mainly distributed in the upper and bottom side of cortical tissue. Although hexose was distributed almost equally throughout the fruits, sucrose was mainly distributed in the upper side of cortical and pith tissues. These results suggest that using the TM-Sprayer in MALDI-IMS was useful for microscopic distribution analysis of anthocyanins, sugars, and organic acids in strawberries.

Characteristics of sugar surfactants in stabilizing proteins during freeze-thawing and freeze-drying.

PubMed

Imamura, Koreyoshi; Murai, Katsuyuki; Korehisa, Tamayo; Shimizu, Noriyuki; Yamahira, Ryo; Matsuura, Tsutashi; Tada, Hiroko; Imanaka, Hiroyuki; Ishida, Naoyuki; Nakanishi, Kazuhiro

2014-06-01

Sugar surfactants with different alkyl chain lengths and sugar head groups were compared for their protein-stabilizing effect during freeze-thawing and freeze-drying. Six enzymes, different in terms of tolerance against inactivation because of freeze-thawing and freeze-drying, were used as model proteins. The enzyme activities that remained after freeze-thawing and freeze-drying in the presence of a sugar surfactant were measured for different types and concentrations of sugar surfactants. Sugar surfactants stabilized all of the tested enzymes both during freeze-thawing and freeze-drying, and a one or two order higher amount of added sugar surfactant was required for achieving protein stabilization during freeze-drying than for the cryoprotection. The comprehensive comparison showed that the C10-C12 esters of sucrose or trehalose were the most effective through the freeze-drying process: the remaining enzyme activities after freeze-thawing and freeze-drying increased at the sugar ester concentrations of 1-10 and 10-100 μM, respectively, and increased to a greater extent than for the other surfactants at higher concentrations. Results also indicate that, when a decent amount of sugar was also added, the protein-stabilizing effect of a small amount of sugar ester through the freeze-drying process could be enhanced. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

14. View to the east up the Sugar River. The ...

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

14. View to the east up the Sugar River. The 1920 enclosed wooden footbridge connected the Chain Machine Building to the company's power plant, pattern shop, and foundry. The Sullivan Machinery Co. Erecting Shop and Machine Shops are in the center of the photo, and the Baltimore truss bridge is visible in the background. - Sullivan Machinery Company, Main Street between Pearl & Water Streets, Claremont, Sullivan County, NH

Physico-chemical properties, wax composition, aroma profiles, and antioxidant activity of granulated non-centrifugal sugars from sugarcane cultivars of Thailand.

PubMed

Weerawatanakorn, Monthana; Asikin, Yonathan; Takahashi, Makoto; Tamaki, Hajime; Wada, Koji; Ho, Chi-Tang; Chuekittisak, Raweewan

2016-11-01

Non-centrifugal cane sugar (NCS) is globally consumed and has various health benefits. It is mostly produced in hardened block form, which is less convenient than in granulated form for food applications. In terms of the traditional processing of NCS, preparation of granulated products is difficult due to the impurities found in the cane juice extracted from the whole stalk. Therefore, the aim of this study was to characterize and determine the physico-chemical properties, wax composition (policosanols and long-chain aldehydes), volatile aroma profiles, and antioxidant activity of traditional NCS in granular form made from four different cane cultivars of Thailand. The total soluble solid, pH, color, and mineral content varied among the sugarcane cultivars, whereas there was no significant difference in the total sugar, phenolic and flavonoid content. The total policosanol, a cholesterol-lowering nutraceutical wax component, and long-chain aldehyde contents were similar in the NCS products amongst three cultivars, and ranged from 2.63 to 3.69 mg/100 g. The granulated NCS products, in which acetaldehyde and dimethyl sulfide were the main volatile compounds, gave less aroma components than traditional NCS. The use of different sugarcane cultivars thus influenced the quality attributes of granulated non-centrifugal sugar products.

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.

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.

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

PubMed

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

2017-07-19

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

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

PubMed

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

1995-01-01

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

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

PubMed

Weininger, Ulrich; Respondek, Michal; Akke, Mikael

2012-09-01

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

Tandem catalysis for the preparation of cylindrical polypeptide brushes.

PubMed

Rhodes, Allison J; Deming, Timothy J

2012-11-28

Here, we report a method for synthesis of cylindrical copolypeptide brushes via N-carboxyanhydride (NCA) polymerization utilizing a new tandem catalysis approach that allows preparation of brushes with controlled segment lengths in a straightforward, one-pot procedure requiring no intermediate isolation or purification steps. To obtain high-density brush copolypeptides, we used a "grafting from" approach where alloc-α-aminoamide groups were installed onto the side chains of NCAs to serve as masked initiators. These groups were inert during cobalt-initiated NCA polymerization and gave allyloxycarbonyl-α-aminoamide-substituted polypeptide main chains. The alloc-α-aminoamide groups were then activated in situ using nickel to generate initiators for growth of side-chain brush segments. This use of stepwise tandem cobalt and nickel catalysis was found to be an efficient method for preparation of high-chain-density, cylindrical copolypeptide brushes, where both the main chains and side chains can be prepared with controlled segment lengths.

CADB: Conformation Angles DataBase of proteins

PubMed Central

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

2003-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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

PubMed

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

2018-03-01

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

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

PubMed

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

2001-02-01

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

Tension amplification in tethered layers of bottle-brush polymers

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

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

2016-02-26

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

Biological and Catalytic Conversion of Sugars and Lignin | Bioenergy | NREL

Science.gov Websites

strings and ribbons twisted on themselves: lilac is labeled "LPMO", red is labeled "Family 5", blue is labeled "Family 6", green is labeled "Family 7", purple is labeled "Family 12", and yellow is labeled "Family 45". Two side-by-side images. The

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

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.

Structure and mechanism of human UDP-xylose synthase: evidence for a promoting role of sugar ring distortion in a three-step catalytic conversion of UDP-glucuronic acid.

PubMed

Eixelsberger, Thomas; Sykora, Sabine; Egger, Sigrid; Brunsteiner, Michael; Kavanagh, Kathryn L; Oppermann, Udo; Brecker, Lothar; Nidetzky, Bernd

2012-09-07

UDP-xylose synthase (UXS) catalyzes decarboxylation of UDP-D-glucuronic acid to UDP-xylose. In mammals, UDP-xylose serves to initiate glycosaminoglycan synthesis on the protein core of extracellular matrix proteoglycans. Lack of UXS activity leads to a defective extracellular matrix, resulting in strong interference with cell signaling pathways. We present comprehensive structural and mechanistic characterization of the human form of UXS. The 1.26-Å crystal structure of the enzyme bound with NAD(+) and UDP reveals a homodimeric short-chain dehydrogenase/reductase (SDR), belonging to the NDP-sugar epimerases/dehydratases subclass. We show that enzymatic reaction proceeds in three chemical steps via UDP-4-keto-D-glucuronic acid and UDP-4-keto-pentose intermediates. Molecular dynamics simulations reveal that the D-glucuronyl ring accommodated by UXS features a marked (4)C(1) chair to B(O,3) boat distortion that facilitates catalysis in two different ways. It promotes oxidation at C(4) (step 1) by aligning the enzymatic base Tyr(147) with the reactive substrate hydroxyl and it brings the carboxylate group at C(5) into an almost fully axial position, ideal for decarboxylation of UDP-4-keto-D-glucuronic acid in the second chemical step. The protonated side chain of Tyr(147) stabilizes the enolate of decarboxylated C(4) keto species ((2)H(1) half-chair) that is then protonated from the Si face at C(5), involving water coordinated by Glu(120). Arg(277), which is positioned by a salt-link interaction with Glu(120), closes up the catalytic site and prevents release of the UDP-4-keto-pentose and NADH intermediates. Hydrogenation of the C(4) keto group by NADH, assisted by Tyr(147) as catalytic proton donor, yields UDP-xylose adopting the relaxed (4)C(1) chair conformation (step 3).

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.

Fragmentation of alpha-Radical Cations of Arginine-Containing Peptides

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

Laskin, Julia; Yang, Zhibo; Ng, Dominic C.

2010-04-01

Fragmentation pathways of peptide radical cations, M+, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of CoIII(salen)-peptide complexes [salen = N,N´-ethylenebis (salicylideneaminato)]. Subsequent hydrogen abstraction from the -carbon of the side chain followed by Ca-C bond cleavage results in the loss of a neutral side chain and formation of an a-radical cation with the radical site localized on the a-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of a-radicals when the basic arginine side chain wasmore » present in the sequence. In contrast, proton-driven fragmentation dominates CID spectra of a-radicals produced via the loss of the arginine side chain. Our results suggest that in most cases radical migration precedes fragmentation of large peptide radical cations.« less

Self-Assembly of Narrowly Dispersed Brush Diblock Copolymers with Domain Spacing more than 100 nm

NASA Astrophysics Data System (ADS)

Gu, Weiyin; Sveinbjornsson, Benjamin; Hong, Sung Woo; Grubbs, Robert; Russell, Thomas

2012-02-01

Self-assembled structures of high molecular weight (MW), narrow molecular weight distribution brush block copolymers containing polylactic acid (PLA) and polystyrene (PS) side chains with similar MWs were studied in both the melt and thin films. The polynorbornene-backbone-based brush diblock copolymers containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing over 100 nm, as revealed by SAXS, GISAXS and AFM. The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state. The length of side chains also played a significant role in terms of controlling the domain size. As the degree of polymerization (DP) increased, the symmetric brush diblock copolymers with longer side chains tended to form larger lamellar microdomains in comparison to those that have the same DP but shorter side chains.

Microscopic insights into the NMR relaxation based protein conformational entropy meter

PubMed Central

Kasinath, Vignesh; Sharp, Kim A.; Wand, A. Joshua

2013-01-01

Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven pro! teins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side-chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion - the NMR-derived generalized order parameters - as a proxy from which to derive changes in protein conformational entropy. PMID:24007504

Stabilization Effect of Amino Acid Side Chains in Peptide Assemblies on Graphite Studied by Scanning Tunneling Microscopy.

PubMed

Guo, Yuanyuan; Hou, Jingfei; Zhang, Xuemei; Yang, Yanlian; Wang, Chen

2017-04-19

An analysis is presented of the effects of amino acid side chains on peptide assemblies in ambient conditions on a graphite surface. The molecularly resolved assemblies of binary peptides are examined with scanning tunneling microscopy. A comparative analysis of the assembly structures reveals that the lamellae width has an appreciable dependence on the peptide sequence, which could be considered as a manifestation of a stabilizing effect of side-chain moieties of amino acids with high (phenylalanine) and low (alanine, asparagine, histidine and aspartic acid) propensities for aggregation. These amino acids are representative for the chemical structures involving the side chains of charged (histidine and aspartic acid), aromatic (phenylalanine), hydrophobic (alanine), and hydrophilic (asparagine) amino acids. These results might provide useful insight for understanding the effects of sequence on the assembly of surface-bound peptides. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isolation of a full-length CC-NBS-LRR resistance gene analog candidate from sugar pine showing low nucleotide diversity.

Treesearch

K.D. Jermstad; L.A. Sheppard; B.B. Kinloch; A. Delfino-Mix; E.S. Ersoz; K.V. Krutovsky; D.B Neale

2006-01-01

The nucleotide-binding-site and leucine-rich-repeat (NBS–LRR) class of R proteins is abundant and widely distributed in plants. By using degenerate primers designed on the NBS domain in lettuce, we amplified sequences in sugar pine that shared sequence identity with many of the NBS–LRR class resistance genes catalogued in GenBank. The polymerase chain reaction products...

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE PAGES

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; ...

2015-11-03

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics

NASA Astrophysics Data System (ADS)

Mansbach, Rachael A.; Ferguson, Andrew L.

2015-03-01

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

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

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Machine learning of single molecule free energy surfaces and the impact of chemistry and environment upon structure and dynamics.

PubMed

Mansbach, Rachael A; Ferguson, Andrew L

2015-03-14

The conformational states explored by polymers and proteins can be controlled by environmental conditions (e.g., temperature, pressure, and solvent) and molecular chemistry (e.g., molecular weight and side chain identity). We introduce an approach employing the diffusion map nonlinear machine learning technique to recover single molecule free energy landscapes from molecular simulations, quantify changes to the landscape as a function of external conditions and molecular chemistry, and relate these changes to modifications of molecular structure and dynamics. In an application to an n-eicosane chain, we quantify the thermally accessible chain configurations as a function of temperature and solvent conditions. In an application to a family of polyglutamate-derivative homopeptides, we quantify helical stability as a function of side chain length, resolve the critical side chain length for the helix-coil transition, and expose the molecular mechanisms underpinning side chain-mediated helix stability. By quantifying single molecule responses through perturbations to the underlying free energy surface, our approach provides a quantitative bridge between experimentally controllable variables and microscopic molecular behavior, guiding and informing rational engineering of desirable molecular structure and function.

Density Functional Study of Stacking Structures and Electronic Behaviors of AnE-PV Copolymer.

PubMed

Dong, Chuan-Ding; Beenken, Wichard J D

2016-10-10

In this work, we report an in-depth investigation on the π-stacking and interdigitating structures of poly(p-anthracene-ethynylene)-alt-poly(p-phenylene-vinylene) copolymer with octyl and ethyl-hexyl side chains and the resulting electronic band structures using density functional theory calculations. We found that in the π-stacking direction, the preferred stacking structure, determined by the steric effect of the branched ethyl-hexyl side chains, is featured by the anthracene-ethynylene units stacking on the phenylene-vinylene units of the neighboring chains and vice versa. This stacking structure, combined with the interdigitating structure where the branched side chains of the laterally neighboring chains are isolated, defines the energetically favorable structure of the ordered copolymer phase, which provides a good compromise between light absorption and charge-carrier transport.

Sugar substitutes: Health controversy over perceived benefits

PubMed Central

Tandel, Kirtida R.

2011-01-01

Sugar is an inseparable part of the food we consume. But too much sugar is not ideal for our teeth and waistline. There have been some controversial suggestions that excessive sugar may play an important role in certain degenerative diseases. So artificial sweeteners or artificially sweetened products continue to attract consumers. A sugar substitute (artificial sweetener) is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Besides its benefits, animal studies have convincingly proven that artificial sweeteners cause weight gain, brain tumors, bladder cancer and many other health hazards. Some kind of health related side effects including carcinogenicity are also noted in humans. A large number of studies have been carried out on these substances with conclusions ranging from “safe under all conditions” to “unsafe at any dose”. Scientists are divided in their views on the issue of artificial sweetener safety. In scientific as well as in lay publications, supporting studies are often widely referenced while the opposing results are de-emphasized or dismissed. So this review aims to explore the health controversy over perceived benefits of sugar substitutes. PMID:22025850

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

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

Adapting Poisson-Boltzmann to the self-consistent mean field theory: Application to protein side-chain modeling

NASA Astrophysics Data System (ADS)

Koehl, Patrice; Orland, Henri; Delarue, Marc

2011-08-01

We present an extension of the self-consistent mean field theory for protein side-chain modeling in which solvation effects are included based on the Poisson-Boltzmann (PB) theory. In this approach, the protein is represented with multiple copies of its side chains. Each copy is assigned a weight that is refined iteratively based on the mean field energy generated by the rest of the protein, until self-consistency is reached. At each cycle, the variational free energy of the multi-copy system is computed; this free energy includes the internal energy of the protein that accounts for vdW and electrostatics interactions and a solvation free energy term that is computed using the PB equation. The method converges in only a few cycles and takes only minutes of central processing unit time on a commodity personal computer. The predicted conformation of each residue is then set to be its copy with the highest weight after convergence. We have tested this method on a database of hundred highly refined NMR structures to circumvent the problems of crystal packing inherent to x-ray structures. The use of the PB-derived solvation free energy significantly improves prediction accuracy for surface side chains. For example, the prediction accuracies for χ1 for surface cysteine, serine, and threonine residues improve from 68%, 35%, and 43% to 80%, 53%, and 57%, respectively. A comparison with other side-chain prediction algorithms demonstrates that our approach is consistently better in predicting the conformations of exposed side chains.

Microbial biodegradation of aromatic alkanoic naphthenic acids is affected by the degree of alkyl side chain branching

PubMed Central

Johnson, Richard J; Smith, Ben E; Sutton, Paul A; McGenity, Terry J; Rowland, Steven J; Whitby, Corinne

2011-01-01

Naphthenic acids (NAs) occur naturally in oil sands and enter the environment through natural and anthropogenic processes. NAs comprise toxic carboxylic acids that are difficult to degrade. Information on NA biodegradation mechanisms is limited, and there are no studies on alkyl branched aromatic alkanoic acid biodegradation, despite their contribution to NA toxicity and recalcitrance. Increased alkyl side chain branching has been proposed to explain NA recalcitrance. Using soil enrichments, we examined the biodegradation of four aromatic alkanoic acid isomers that differed in alkyl side chain branching: (4′-n-butylphenyl)-4-butanoic acid (n-BPBA, least branched); (4′-iso-butylphenyl)-4-butanoic acid (iso-BPBA); (4′-sec-butylphenyl)-4-butanoic acid (sec-BPBA) and (4′-tert-butylphenyl)-4-butanoic acid (tert-BPBA, most branched). n-BPBA was completely metabolized within 49 days. Mass spectral analysis confirmed that the more branched isomers iso-, sec- and tert-BPBA were transformed to their butylphenylethanoic acid (BPEA) counterparts at 14 days. The BPEA metabolites were generally less toxic than BPBAs as determined by Microtox assay. n-BPEA was further transformed to a diacid, showing that carboxylation of the alkyl side chain occurred. In each case, biodegradation of the carboxyl side chain proceeded through beta-oxidation, which depended on the degree of alkyl side chain branching, and a BPBA degradation pathway is proposed. Comparison of 16S rRNA gene sequences at days 0 and 49 showed an increase and high abundance at day 49 of Pseudomonas (sec-BPBA), Burkholderia (n-, iso-, tert-BPBA) and Sphingomonas (n-, sec-BPBA). PMID:20962873

[Studies on separation, purification and structure characteristics of a polysaccharide LTC-II from Pyrola corbieri].

PubMed

Mo, Zhengchang; Wu, Lanfang; Yang, Juan; Wang, Daoping

2011-06-01

To characterize the structure of polysaccharide LTC-II obtained from Pyrola corbieri. The polysaccharide was extracted from P. corbieri by hot water and ethanol precipitation. Crude polysaccharide was purified by DEAE-Cellulose chromatography and Sephacryl S-300 HR column chromatography. The purity and molecular weight of polysaccharide was determined by gel permeation chromatography. UV, IR, optical rotation, complete acid hydrolysis, periodate oxydation, Smith degradation, partial acid hydrolysis and methylation analysis were applied to determine the structural features. A homogeneous fraction LTC-II was obtained and its relative molecular mass was 22 000 Da. It consisted of arabinose, mannose, glucose, galactose in the molar ratio of 35. 2: 1.0: 13. 4: 4. 2. LTC-II had a backbone consisting glucose, mannose, galactose and mainly contained (1 --> 6)-linkaged glucose. The side chain possessed arabinose, glucose, galactose and mainly contained (1 --> 5)-linkaged arabinose. The terminal sugar were mainly glucose and galactose. Studies on the preliminary characterization of polysaccharide LTC-II from P. corbieri for the first time.

Glycation of H1 Histone by 3-Deoxyglucosone: Effects on Protein Structure and Generation of Different Advanced Glycation End Products

PubMed Central

Ashraf, Jalaluddin Mohammad; Rabbani, Gulam; Ahmad, Saheem; Hasan, Qambar; Khan, Rizwan Hasan; Alam, Khursheed; Choi, Inho

2015-01-01

Advanced glycation end products (AGEs) culminate from the non-enzymatic reaction between a free carbonyl group of a reducing sugar and free amino group of proteins. 3-deoxyglucosone (3-DG) is one of the dicarbonyl species that rapidly forms several protein-AGE complexes that are believed to be involved in the pathogenesis of several diseases, particularly diabetic complications. In this study, the generation of AGEs (Nε-carboxymethyl lysine and pentosidine) by 3-DG in H1 histone protein was characterized by evaluating extent of side chain modification (lysine and arginine) and formation of Amadori products as well as carbonyl contents using several physicochemical techniques. Results strongly suggested that 3-DG is a potent glycating agent that forms various intermediates and AGEs during glycation reactions and affects the secondary structure of the H1 protein. Structural changes and AGE formation may influence the function of H1 histone and compromise chromatin structures in cases of secondary diabetic complications. PMID:26121680

O-Acetyl location on cepacian, the principal exopolysaccharide of Burkholderia cepacia complex bacteria.

PubMed

Cescutti, Paola; Impallomeni, Giuseppe; Garozzo, Domenico; Rizzo, Roberto

2011-12-27

Cepacian is an exopolysaccharide produced by the majority of the isolates belonging to the Burkholderia cepacia complex bacteria, a group of 17 species, some of which infect cystic fibrosis patients, sometime with fatal outcome. The repeating unit of cepacian consists of a backbone having a trisaccharidic repeating unit with three side chains, as reported in the formula below. The exopolysaccharide is also acetylated, carrying from one to three acetyl esters per repeating unit, depending on the strain examined. The consequences of O-acetyl substitution in a polysaccharide are important both for its biological functions and for industrial applications, including the preparation of conjugated vaccines, since O-acetyl groups are important immunogenic determinants. The location of acetyl groups was achieved by NMR spectroscopy and ESI mass spectrometry and revealed that these substituents are scattered in non-stoichiometric ratio on many sugar residues in different positions, a feature which adds to the already unique carbohydrate structure of the polysaccharide. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure elucidation of a bioactive polysaccharide from fruiting bodies of Hericium erinaceus in different maturation stages.

PubMed

Li, Qiao-Zhen; Wu, Di; Zhou, Shuai; Liu, Yan-Fang; Li, Zheng-Peng; Feng, Jie; Yang, Yan

2016-06-25

HPB-3, a heteropolysaccharide, with a mean molecular weight of 1.5×10(4)Da, was obtained from the maturating-stage IV, V and VI fruiting body of Hericium erinaceus, exhibited higher macrophages stimulation activities, was able to upregulate the functional events mediated by activated macrophages, such as production of nitric oxide (NO). Monosaccharide composition analysis showed that HPB-3 comprised l-fucose, d-galactose and d-glucose in the ratio of 5.2:23.9:1. Its chemical structure was characterized by sugar and methylation analysis, along with (1)H and (13)C NMR spectroscopy, including (1)H-(1)H COSY, TOCSY, NOESY, HMQC and HMBC experiments. The results indicated that HPB-3 contained a-(1/6)-linked galactopyranosyl backbone, partially with a side chain composed of α-l-fucopyranose at the O-2 position. The predicted primary structure of the polysaccharide was established as below. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immobilization of paracetamol and benzocaine pro-drug derivatives as long-range self-organized monolayers on graphite.

PubMed

Popoff, Alexandre; Fichou, Denis

2008-05-01

We show here by means of scanning tunneling microscopy (STM) at the liquid/solid interface that paracetamol and benzocaine molecules bearing a long aliphatic chain can be immobilized on highly oriented pyrolitic graphite (HOPG) as perfectly ordered two-dimensional domains extending over several hundreds of nanometers. In both cases, high-resolution STM images reveal that compounds 1 and 2 self-assemble into parallel lamellae having a head-to-head arrangement. The paracetamol heads of 1 are in a zigzag position with entangled n-dodecyloxy side chains while benzocaine heads of compound 2 are perfectly aligned as a double row and have their palmitic side chains on either sides of the head alignment. We attribute the very long-range ordering of these two pro-drug derivatives on HOPG to the combined effects of intermolecular H-bonding on one side and Van der Waals interactions between aliphatic side chains and graphite on the other side. The 2D immobilization of pro-drug derivatives via a non-destructive physisorption mechanism could prove to be useful for applications such as drug delivery if it can be realized on a biocompatible substrate.

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.

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

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

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

2010-03-05

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

Scale-Dependent Stiffness and Internal Tension of a Model Brush Polymer

NASA Astrophysics Data System (ADS)

Berezney, John P.; Marciel, Amanda B.; Schroeder, Charles M.; Saleh, Omar A.

2017-09-01

Bottle-brush polymers exhibit closely grafted side chains that interact by steric repulsion, thereby causing stiffening of the main polymer chain. We use single-molecule elasticity measurements of model brush polymers to quantify this effect. We find that stiffening is only significant on long length scales, with the main chain retaining flexibility on short scales. From the elasticity data, we extract an estimate of the internal tension generated by side-chain repulsion; this estimate is consistent with the predictions of blob-based scaling theories.

The Inherent Conformational Preferences of Glutamine-Containing Peptides: the Role for Side-Chain Backbone Hydrogen Bonds

NASA Astrophysics Data System (ADS)

Walsh, Patrick S.; McBurney, Carl; Gellman, Samuel H.; Zwier, Timothy S.

2015-06-01

Glutamine is widely known to be found in critical regions of peptides which readily fold into amyloid fibrils, the structures commonly associated with Alzheimer's disease and glutamine repeat diseases such as Huntington's disease. Building on previous single-conformation data on Gln-containing peptides containing an aromatic cap on the N-terminus (Z-Gln-OH and Z-Gln-NHMe), we present here single-conformation UV and IR spectra of Ac-Gln-NHBn and Ac-Ala-Gln-NHBn, with its C-terminal benzyl cap. These results point towards side-chain to backbone hydrogen bonds dominating the structures observed in the cold, isolated environment of a molecular beam. We have identified and assigned three main conformers for Ac-Gln-NHBn all involving primary side-chain to backbone interactions. Ac-Ala-Gln-NHBn extends the peptide chain by one amino acid, but affords an improvement in the conformational flexibility. Despite this increase in the flexibility, only a single conformation is observed in the gas-phase: a structure which makes use of both side-chain-to-backbone and backbone-to-backbone hydrogen bonds.

Mucopolysaccharidosis type III

MedlinePlus

... the enzymes needed to break down the heparan sulfate sugar chain are missing or defective. There are ... a large amount of a mucopolysaccharide called heparan sulfate in the urine. Other tests may include: Blood ...

Gemini analogs of vitamin D.

PubMed

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

2014-01-01

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

Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain

PubMed Central

Iwaniuk, Daniel P.; Whetmore, Eric D.; Rosa, Nicholas; Ekoue-Kovi, Kekeli; Alumasa, John; de Dios, Angel C.; Roepe, Paul D.; Wolf, Christian

2009-01-01

We report the synthesis and in vitro antimalarial activity of several new 4-amino-and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of P. falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11–15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain. PMID:19703776

Polymer composites containing nanotubes

NASA Technical Reports Server (NTRS)

Bley, Richard A. (Inventor)

2008-01-01

The present invention relates to polymer composite materials containing carbon nanotubes, particularly to those containing singled-walled nanotubes. The invention provides a polymer composite comprising one or more base polymers, one or more functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers and carbon nanotubes. The invention also relates to functionalized m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers, particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having side chain functionalization, and more particularly to m-phenylenevinylene-2,5-disubstituted-p-phenylenevinylene polymers having olefin side chains and alkyl epoxy side chains. The invention further relates to methods of making polymer composites comprising carbon nanotubes.

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.

Gas-phase spectroscopy of synephrine by laser desorption supersonic jet technique.

PubMed

Ishiuchi, Shun-ichi; Asakawa, Toshiro; Mitsuda, Haruhiko; Miyazaki, Mitsuhiko; Chakraborty, Shamik; Fujii, Masaaki

2011-09-22

In our previous work, we found that synephrine has six conformers in the gas phase, while adrenaline, which is a catecholamine and has the same side chain as synephrine, has been reported to have only two conformers. To determine the conformational geometries of synephrine, we measured resonance enhanced multiphoton ionization, ultraviolet-ultraviolet hole burning, and infrared dip spectra by utilizing the laser desorption supersonic jet technique. By comparing the observed infrared spectra with theoretical ones, we assigned geometries except for the orientations of the phenolic OH group. Comparison between the determined structures of synephrine and those of 2-methylaminno-1-phenylethanol, which has the same side chain as synephrine but no phenol OH group, leads to the conclusion that the phenolic OH group in synephrine does not affect the conformational flexibility of the side chain. In the case of adrenaline, which is expected to have 12 conformers if there are no interactions between the catecholic OH groups and the side chain, some interactions possibly exist between them because only two conformations are observed. By estimation of the dipole-dipole interaction energy between partial dipole moments of the catecholic OH groups and the side chain, it was concluded that the dipole-dipole interaction stabilizes specific conformers which are actually observed. © 2011 American Chemical Society

Empirical parameterization of a model for predicting peptide helix/coil equilibrium populations.

PubMed Central

Andersen, N. H.; Tong, H.

1997-01-01

A modification of the Lifson-Roig formulation of helix/coil transitions is presented; it (1) incorporates end-capping and coulombic (salt bridges, hydrogen bonding, and side-chain interactions with charged termini and the helix dipole) effects, (2) helix-stabilizing hydrophobic clustering, (3) allows for different inherent termination probabilities of individual residues, and (4) differentiates helix elongation in the first versus subsequent turns of a helix. Each residue is characterized by six parameters governing helix formation. The formulation of the conditional probability of helix initiation and termination that we developed is essentially the same as one presented previously (Shalongo W, Stellwagen, E. 1995. Protein Sci 4:1161-1166) and nearly the mathematical equivalent of the new capping formulation incorporated in the model presented by Rohl et al. (1996. Protein Sci 5:2623-2637). Side-chain/side-chain interactions are, in most cases, incorporated as context dependent modifications of propagation rather than nucleation parameters. An alternative procedure for converting [theta]221 values to experimental fractional helicities () is presented. Tests of the program predictions suggest this method may have some advantages both for designed peptides and for the analysis of secondary structure preferences that could drive the formation of molten-globule intermediates on protein folding pathways. The model predicts the fractional helicity of 385 peptides with a root-mean-square deviation (RMSD) of 0.050 and locates (with precise definition of the termini in many cases) helices in proteins as well as competing methods. The propagation and nucleation parameters were derived from NMR data and from the CD data for a 79 peptide "learning set" for which an excellent fit resulted (RMSD = 0.0295). The current set of parameter corrections for capping boxes, helix dipole interactions, and side-chain/side-chain interactions (coulombic, hydrogen bonding and hydrophobic clustering), although still under development provide a significant improvement in both helix/coil equilibrium prediction for peptides and helix location in protein sequences. This is clearly evident in the rms deviations between CD measures and calculated values of fractional helicity for different classes of peptides before and after applying the corrections: for peptides lacking capping boxes and i/i + 3 and i/i + 4 side-chain/side-chain interactions RMSD = 0.044 (n = 164) versus RMSD = 0.054 (0.172 without the corrections, n = 221) for peptides that required context-dependent corrections of the parameters. If we restrict the analysis to N-acylated peptides with helix stabilizing side-chain/side-chain interactions (including N-capping boxes), the degree to which our corrections account for the stabilizing interaction can be judged from the change in helicity underestimation, (calc-CD): -0.15 +/- 0.10, which is reduced to -0.018 +/- 0.048 (n = 191) upon applying the corrections. PMID:9300492

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS)☟

PubMed Central

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M.; Ioerger, Thomas R.; Burgess, Kevin

2013-01-01

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, “minimalist helical mimics”. It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i+4, i+7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i+3, i+7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds;(iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain “triads” in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the “side-chain correspondences” (eg i, i+4, i+7 or i, i+3, i+4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1 – 8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites. PMID:24121516

Evaluating minimalist mimics by exploring key orientations on secondary structures (EKOS).

PubMed

Xin, Dongyue; Ko, Eunhwa; Perez, Lisa M; Ioerger, Thomas R; Burgess, Kevin

2013-11-28

Peptide mimics that display amino acid side-chains on semi-rigid scaffolds (not peptide polyamides) can be referred to as minimalist mimics. Accessible conformations of these scaffolds may overlay with secondary structures giving, for example, "minimalist helical mimics". It is difficult for researchers who want to apply minimalist mimics to decide which one to use because there is no widely accepted protocol for calibrating how closely these compounds mimic secondary structures. Moreover, it is also difficult for potential practitioners to evaluate which ideal minimalist helical mimics are preferred for a particular set of side-chains. For instance, what mimic presents i, i + 4, i + 7 side-chains in orientations that best resemble an ideal α-helix, and is a different mimic required for a i, i + 3, i + 7 helical combination? This article describes a protocol for fitting each member of an array of accessible scaffold conformations on secondary structures. The protocol involves: (i) use quenched molecular dynamics (QMD) to generate an ensemble consisting of hundreds of accessible, low energy conformers of the mimics; (ii) representation of each of these as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; (iii) similar representation of each combination of three side-chains in each ideal secondary structure as a set of Cα and Cβ coordinates corresponding to three amino acid side-chains displayed by the scaffolds; and, (iv) overlay Cα and Cβ coordinates of all the conformers on all the sets of side-chain "triads" in the ideal secondary structures and express the goodness of fit in terms of root mean squared deviation (RMSD, Å) for each overlay. We refer to this process as Exploring Key Orientations on Secondary structures (EKOS). Application of this procedure reveals the relative bias of a scaffold to overlay on different secondary structures, the "side-chain correspondences" (e.g. i, i + 4, i + 7 or i, i + 3, i + 4) of those overlays, and the energy of this state relative to the minimum located. This protocol was tested on some of the most widely cited minimalist α-helical mimics (1-8 in the text). The data obtained indicates several of these compounds preferentially exist in conformations that resemble other secondary structures as well as α-helices, and many of the α-helical conformations have unexpected side-chain correspondences. These observations imply the featured minimalist mimics have more scope for disrupting PPI interfaces than previously anticipated. Finally, the same simulation method was used to match preferred conformations of minimalist mimics with actual protein/peptide structures at interfaces providing quantitative comparisons of predicted fits of the test mimics at protein-protein interaction sites.

Device and method to relieve cordelle action in a chain driven pump

DOEpatents

Dysarz, Edward D.

1994-01-01

A cordelle action relief apparatus or device for use in sucker rod pumps in a petroleum or water well. The device is incorporated in a chain driven pump to prevent the chain from forming a bow or archlike configuration as the chain rolls off of the sprocket and down into the well. When the chain is allowed to form this bow or arch it could damage the well and well casing. The device includes a first rod on the side of the chain and a second rod on the second side of the chain that will allow the rollers of the chain to roll on the rod and further prevent the chain from bowing or arching and will further allow the rollers on the chain to roll on the rods which will further prevent damage to the well casing, the well, and the chain.

Dihydroresveratrol Type Dihydrostilbenoids: Chemical Diversity, Chemosystematics, and Bioactivity.

PubMed

Vitalini, Sara; Cicek, Serhat S; Granica, Sebastian; Zidorn, Christian

2018-01-01

Dihydrostilbenoids, a diverse class of natural products differing from stilbenoids by the missing double bond in the ethylene chain linking the aromatic moieties, have been reported from fungi, mosses, ferns, and flowering plants. Occurrence, structure, and bioactivity of naturally occurring dihydroresveratrol type dihydrostilbenoids are discussed in this review. A Reaxys database search for dihydroresveratrol derivatives with possible substitutions on all atoms, but excluding non-natural products and compounds featuring additional rings involving the ethyl connecting chain, was performed. Structures include simple dihydroresveratrol derivatives, compounds substituted with complex side chains composed of acyl moieties and sugars, and compounds containing polycyclic cores attached to dihydrostilbenoid units. Dihydrostilbenoids have a wide spectrum of bioactivities ranging from expectable antioxidant and anti-inflammatory activities to interesting neuroprotective and anticancer activity. The anticancer activity in particular is very pronounced for some plant-derived dihydrostilbenoids and makes them interesting lead compounds for drug development. Apart from some reports on dihydroresveratrol derivatives as phytoalexins against plant-pathogenic fungi, only very limited information is available on the ecological role of these compounds for the organisms producing them. Dihydrostilbenoids are a class of natural products possessing significant biological activities; their scattered but not ubiquitous occurrence throughout the kingdoms of plants and fungi is not easily explained. We are convinced that future studies will identify new sources of dihydrostilbenoids, and we hope that the present review will inspire such studies and will help in directing such efforts to suitable source organisms and towards promising bioactivities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

PubMed

Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Dynamics of Polarons in Organic Conjugated Polymers with Side Radicals.

PubMed

Liu, J J; Wei, Z J; Zhang, Y L; Meng, Y; Di, B

2017-03-16

Based on the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model, and using the molecular dynamics method, we discuss the dynamics of electron and hole polarons propagating along a polymer chain, as a function of the distance between side radicals and the magnitude of the transfer integrals between the main chain and the side radicals. We first discuss the average velocities of electron and hole polarons as a function of the distance between side radicals. It is found that the average velocities of the electron polarons remain almost unchanged, while the average velocities of hole polarons decrease significantly when the radical distance is comparable to the polaron width. Second, we have found that the average velocities of electron polarons decrease with increasing transfer integral, but the average velocities of hole polarons increase. These results may provide a theoretical basis for understanding carriers transport properties in polymers chain with side radicals.

Highly Stable, Anion Conductive, Comb-Shaped Copolymers for Alkaline Fuel Cells

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

Li, NW; Leng, YJ; Hickner, MA

2013-07-10

To produce an anion-conductive and durable polymer electrolyte for alkaline fuel cell applications, a series of quaternized poly(2,6-dimethyl phenylene oxide)s containing long alkyl side chains pendant to the nitrogen-centered cation were synthesized using a Menshutkin reaction to form comb-shaped structures. The pendant alkyl chains were responsible for the development of highly conductive ionic domains, as confirmed by small-angle X-ray scattering (SAXS). The comb-shaped polymers having one alkyl side chain showed higher hydroxide conductivities than those with benzyltrimethyl ammonium moieties or structures with more than one alkyl side chain per cationic site. The highest conductivity was observed for comb-shaped polymers withmore » benzyldimethylhexadecyl ammonium cations. The chemical stabilities of the comb-shaped membranes were evaluated under severe, accelerated-aging conditions, and degradation was observed by measuring IEC and ion conductivity changes during aging. The comb-shaped membranes retained their high ion conductivity in 1 M NaOH at 80 degrees C for 2000 h. These cationic polymers were employed as ionomers in catalyst layers for alkaline fuel cells. The results indicated that the C-16 alkyl side chain ionomer had a slightly better initial performance, despite its low IEC value, but very poor durability in the fuel cell. In contrast, 90% of the initial performance was retained for the alkaline fuel cell with electrodes containing the C-6 side chain after 60 h of fuel cell operation.« less

In silico molecular engineering for a targeted replacement in a tumor-homing peptide

PubMed Central

Zanuy, David; Flores-Ortega, Alejandra; Jiménez, Ana I.; Calaza, M. Isabel; Cativiela, Carlos; Nussinov, Ruth; Ruoslahti, Erkki; Alemán, Carlos

2009-01-01

A new amino acid has been designed as a replacement for arginine (Arg, R) to protect the tumor-homing pentapeptide CREKA from proteases. This amino acid, denoted (Pro)hArg, is characterized by a proline skeleton bearing a specifically oriented guanidinium side chain. This residue combines the ability of Pro to induce turn-like conformations with the Arg side-chain functionality. The conformational profile of the CREKA analogue incorporating this Arg substitute has been investigated by a combination of simulated annealing and Molecular Dynamics. Comparison of the results with those previously obtained for the natural CREKA shows that (Pro)hArg significantly reduces the conformational flexibility of the peptide. Although some changes are observed in the backbone···backbone and side chain···side chain interactions, the modified peptide exhibits a strong tendency to accommodate turn conformations centered at the (Pro)hArg residue and the overall shape of the molecule in the lowest energy conformations characterized for the natural and the modified peptide exhibit a high degree of similarity. In particular, the turn orients the backbone such that the Arg, Glu and Lys side chains face the same side of the molecule, which is considered essential for bioactivity. These results suggest that replacement of Arg by (Pro)hArg in CREKA may be useful in providing resistance against proteolytic enzymes while retaining conformational features which are essential for tumor-homing activity. PMID:19432404

Mass spectrometric method to determine the chain length of oligosaccharides attached to phenolic polymers by nonglycosidic linkages

Treesearch

James L. Minor; Roger C. Pettersen

1987-01-01

In many plants, a portion of the polysaccharides appears to have a very low degree of cross-linking with aromatic polymers such as lignin or flavolans. The proportion of cross-linked units may be enriched for study by enzymatically hydrolyzing the nonbonded carbohydrates. A convenient method is described for the simultaneous analysis of sugar content and apparent chain...

A solid-state NMR study of the dynamics and interactions of phenylalanine rings in a statherin fragment bound to hydroxyapatite crystals.

PubMed

Gibson, James M; Popham, Jennifer M; Raghunathan, Vinodhkumar; Stayton, Patrick S; Drobny, Gary P

2006-04-26

Extracellular matrix proteins regulate hard tissue growth by acting as adhesion sites for cells, by triggering cell signaling pathways, and by directly regulating the primary and/or secondary crystallization of hydroxyapatite, the mineral component of bone and teeth. Despite the key role that these proteins play in the regulation of hard tissue growth in humans, the exact mechanism used by these proteins to recognize mineral surfaces is poorly understood. Interactions between mineral surfaces and proteins very likely involve specific contacts between the lattice and the protein side chains, so elucidation of the nature of interactions between protein side chains and their corresponding inorganic mineral surfaces will provide insight into the recognition and regulation of hard tissue growth. Isotropic chemical shifts, chemical shift anisotropies (CSAs), NMR line-width information, (13)C rotating frame relaxation measurements, as well as direct detection of correlations between (13)C spins on protein side chains and (31)P spins in the crystal surface with REDOR NMR show that, in the peptide fragment derived from the N-terminal 15 amino acids of salivary statherin (i.e., SN-15), the side chain of the phenylalanine nearest the C-terminus of the peptide (F14) is dynamically constrained and oriented near the surface, whereas the side chain of the phenylalanine located nearest to the peptide's N-terminus (F7) is more mobile and is oriented away from the hydroxyapatite surface. The relative dynamics and proximities of F7 and F14 to the surface together with prior data obtained for the side chain of SN-15's unique lysine (i.e., K6) were used to construct a new picture for the structure of the surface-bound peptide and its orientation to the crystal surface.

Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the HDL receptor SR-BI

PubMed Central

Yu, Miao; Lau, Thomas Y.; Carr, Steven A.; Krieger, Monty

2013-01-01

The high density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys321-Pro322-Cys323 (CPC) motif and connect Cys280 to Cys334. We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys384 to HDL binding and lipid uptake. The effects of CPC mutations on activity were context dependent. Full wild-type (WT) activity required Pro322 and Cys323 only when Cys321 was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX or XXX mutants (X≠WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys323 is deleterious, perhaps because of aberrant disulfide bond formation. Pro322 may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for activity. C384X (X=S,T,L,Y,G,A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (increased binding, decreased uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C384X mutants were BLT-1 resistant, supporting the proposal that Cys384's thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories. PMID:23205738

Designing and Creating a Synthetic Omega Oxidation Pathway in Saccharomyces cerevisiae Enables Production of Medium-Chain α, ω-Dicarboxylic Acids

PubMed Central

Han, Li; Peng, Yanfeng; Zhang, Yuangyuan; Chen, Wujiu; Lin, Yuping; Wang, Qinhong

2017-01-01

Medium-chain (C8–C14) α, ω-dicarboxylic acids (α, ω-DCAs), which have numerous applications as raw materials for producing various commodities and polymers in chemical industry, are mainly produced from chemical or microbial conversion of petroleum-derived alkanes or plant-derived fatty acids at present. Recently, significant attention has been gained to microbial production of medium-chain α, ω-DCAs from simple renewable sugars. Here, we designed and created a synthetic omega oxidation pathway in Saccharomyces cerevisiae to produce C10 and C12 α, ω-DCAs from renewable sugars and fatty acids by introducing a heterogeneous cytochrome P450 CYP94C1 and cytochrome reductase ATR1. Furthermore, the deletion of fatty acyl-CoA synthetase genes FAA1 and FAA4 increased the production of medium-chain α, ω-DCAs from 4.690 ± 0.088 mg/L to 12.177 ± 0.420 mg/L and enabled the production of C14 and C16 α, ω-DCAs at low percentage. But blocking β-oxidation pathway by deleting fatty-acyl coenzyme A oxidase gene POX1 and overexpressing different thioesterase genes had no significant impact on the production and the composition of α, ω-dicarboxylic acids. Overall, our study indicated the potential of microbial production of medium-chain α, ω-DCAs from renewable feedstocks using engineered yeast. PMID:29163455

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.

G-protein gamma subunit 1 is required for sugar reception in Drosophila

PubMed Central

Ishimoto, Hiroshi; Takahashi, Kuniaki; Ueda, Ryu; Tanimura, Teiichi

2005-01-01

Though G-proteins have been implicated in the primary step of taste signal transduction, no direct demonstration has been done in insects. We show here that a G-protein gamma subunit, Gγ1, is required for the signal transduction of sugar taste reception in Drosophila. The Gγ1 gene is expressed mainly in one of the gustatory receptor neurons. Behavioral responses of the flies to sucrose were reduced by the targeted suppression of neural functions of Gγ1-expressing cells using neural modulator genes such as the modified Shaker K+ channel (EKO), the tetanus toxin light chain or the shibire (shits1) gene. RNA interference targeting to the Gγ1 gene reduced the amount of Gγ1 mRNA and suppressed electrophysiological response of the sugar receptor neuron. We also demonstrated that responses to sugars were lowered in Gγ1 null mutant, Gγ1N159. These results are consistent with the hypothesis that Gγ1 participates in the signal transduction of sugar taste reception. PMID:16121192

Synthesis and Characterization of Itaconic Anhydride and Stearyl Methacrylate Copolymers

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

Shang, S.; Huang, S; Weiss, R

The free-radical copolymerization and the properties of comb-like copolymers derived from renewable resources, itaconic anhydride (ITA) and stearyl methacrylate (SM), are described. The ITA-SM copolymers were nearly random with a slight alternating tendency. The copolymers exhibited a nanophase-separated morphology, with the stearate side-chains forming a bilayer, semi-crystalline structure. The melting point (Tm) of the side-chains and the crystallinity decreased with increasing ITA concentration. The crystalline side-chains suppressed molecular motion of the main chain, so that a glass transition temperature (Tg) was not resolved unless the ITA concentration was sufficiently high so that Tg > Tm. The softening point and modulusmore » of the copolymers increased with the increasing ITA concentration, but the thermal stability decreased.« less

Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies.

PubMed

Lavrado, João; Cabal, Ghislain G; Prudêncio, Miguel; Mota, Maria M; Gut, Jiri; Rosenthal, Philip J; Díaz, Cecília; Guedes, Rita C; dos Santos, Daniel J V A; Bichenkova, Elena; Douglas, Kenneth T; Moreira, Rui; Paulo, Alexandra

2011-02-10

The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial and cytotoxicity properties are reported. Propyl, butyl, and cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing cytotoxicity when compared with the parent compound. Localization studies inside parasite blood stages by fluorescence microscopy showed that these derivatives accumulate inside the nucleus, indicating that the incorporation of a basic side chain is not sufficient enough to promote selective accumulation in the acidic digestive vacuole of the parasite. Most of the compounds within this series showed the ability to bind to a double-stranded DNA duplex as well to monomeric hematin, suggesting that these are possible targets associated with the observed antimalarial activity. Overall, these novel cryptolepine analogues with substantially improved antiplasmodial activity and selectivity index provide a promising starting point for development of potent and highly selective agents against drug-resistant malaria parasites.

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

PubMed Central

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

2009-01-01

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

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

PubMed

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

2008-06-26

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

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

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

Pectin-rich biomass as feedstock for fuel ethanol production.

PubMed

Edwards, Meredith C; Doran-Peterson, Joy

2012-08-01

The USA has proposed that 30 % of liquid transportation fuel be produced from renewable resources by 2030 (Perlack and Stokes 2011). It will be impossible to reach this goal using corn kernel-based ethanol alone. Pectin-rich biomass, an under-utilized waste product of the sugar and juice industry, can augment US ethanol supplies by capitalizing on this already established feedstock. Currently, pectin-rich biomass is sold (at low value) as animal feed. This review focuses on the three most studied types of pectin-rich biomass: sugar beet pulp, citrus waste and apple pomace. Fermentations of these materials have been conducted with a variety of ethanologens, including yeasts and bacteria. Escherichia coli can ferment a wide range of sugars including galacturonic acid, the primary component of pectin. However, the mixed acid metabolism of E. coli can produce unwanted side products. Saccharomyces cerevisiae cannot naturally ferment galacturonic acid nor pentose sugars but has a homoethanol pathway. Erwinia chrysanthemi is capable of degrading many of the cell wall components of pectin-rich materials, including pectin. Klebsiella oxytoca can metabolize a diverse array of sugars including cellobiose, one degradation product of cellulose. However, both E. chrysanthemi and K. oxytoca produce side products during fermentation, similar to E. coli. Using pectin-rich residues from industrial processes is beneficial because the material is already collected and partially pretreated to facilitate enzymatic deconstruction of the plant cell walls. Using biomass already produced for other purposes is an attractive practice because fewer greenhouse gases (GHG) will be anticipated from land-use changes.

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

PubMed

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

2000-01-07

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

Molecular design of anti-MRSA agents based on the anacardic acid scaffold.

PubMed

Green, Ivan R; Tocoli, Felismino E; Lee, Sang Hwa; Nihei, Ken-Ichi; Kubo, Isao

2007-09-15

A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6-(4',8'-dimethylnonyl)salicylic acid, and the alicyclic side-chain analogue, 6-cyclododecylmethyl salicylic acid, with the minimum inhibitory concentration (MIC) of 0.39 microg/mL, respectively. This activity was superior to that of the most potent antibacterial anacardic acid isolated from the cashew Anacardium occidentale (Anacardiaceae), apple and nut, that is, the 6-[8'(Z),11'(Z),14'-pentadecatrienyl]salicylic acid.

Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain.

PubMed

Nakajima, Ryo; Yamamoto, Naoshi; Hirayama, Shigeto; Iwai, Takashi; Saitoh, Akiyoshi; Nagumo, Yasuyuki; Fujii, Hideaki; Nagase, Hiroshi

2015-10-01

We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a β-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine. Copyright © 2015 Elsevier Ltd. All rights reserved.

BetaSCPWeb: side-chain prediction for protein structures using Voronoi diagrams and geometry prioritization

PubMed Central

Ryu, Joonghyun; Lee, Mokwon; Cha, Jehyun; Laskowski, Roman A.; Ryu, Seong Eon; Kim, Deok-Soo

2016-01-01

Many applications, such as protein design, homology modeling, flexible docking, etc. require the prediction of a protein's optimal side-chain conformations from just its amino acid sequence and backbone structure. Side-chain prediction (SCP) is an NP-hard energy minimization problem. Here, we present BetaSCPWeb which efficiently computes a conformation close to optimal using a geometry-prioritization method based on the Voronoi diagram of spherical atoms. Its outputs are visual, textual and PDB file format. The web server is free and open to all users at http://voronoi.hanyang.ac.kr/betascpweb with no login requirement. PMID:27151195

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.

Mexico-U.S. Relations: Issues for the 109th Congress

DTIC Science & Technology

2005-06-02

argues that a sugar side letter negotiated along with NAFTA limits Mexican shipments of sugar. Mexico also complains that imports of high fructose ... corn syrup (HFCS) sweeteners from the United States constitute dumping, and it imposed anti- dumping duties for some time, even though NAFTA and WTO...imports from the United States. In the last days of 2001, the Mexican Congress imposed a 20% tax on soft drinks made with corn syrup sweeteners to aid the

U.S.-Mexico Economic Relations: Trends, Issues, and Implications

DTIC Science & Technology

2009-04-03

and high fructose corn syrup . Mexico argued that the sugar side letter negotiated under NAFTA entitled it to ship net sugar surplus to the United...that imports of high fructose corn syrup (HFCS) sweeteners from the United States constituted dumping, and it imposed anti-dumping duties for some time...industries to restrict HFCS imports from the United States. In late 2001, the Mexican Congress imposed a 20% tax on soft drinks made with corn syrup

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

NASA Astrophysics Data System (ADS)

Madkour, Tarek M.

2013-08-01

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

Conformational Changes of Bovine Serum Albumin Induced by Adsorption on Different Clay Surfaces: FTIR Analysis.

PubMed

Servagent-Noinville; Revault; Quiquampoix; Baron

2000-01-15

Interactions between proteins and clays perturb biological activity in ecosystems, particularly soil extracellular enzyme activity. The pH dependence of hydrophobic, hydrophilic, and electrostatic interactions on the adsorption of bovine serum albumin (BSA) is studied. BSA secondary structures and hydration are revealed from computation of the Amide I and II FTIR absorption profiles. The influence of ionization of Asp, Glu, and His side chains on the adsorption processes is deduced from correlation between p(2)H dependent carboxylic/carboxylate ratio and Amide band profiles. We quantify p(2)H dependent internal and external structural unfolding for BSA adsorbed on montmorillonite, which is an electronegative phyllosilicate. Adsorption on talc, a hydrophobic surface, is less denaturing. The results emphasize the importance of electrostatic interactions in both adsorption processes. In the first case, charged side chains directly influence BSA adsorption that generate the structural transition. In the second case, the forces that attract hydrophobic side chains toward the protein-clay interface are large enough to distort peripheral amphiphilic helical domains. The resulting local unfolding displaces enough internal ionized side chains to prevent them from establishing salt bridges as for BSA native structure in solution. On montmorillonite, a particular feature is a higher protonation of the Asp and Glu side chains of the adsorbed BSA than in solution, which decreases coulombic repulsion. Copyright 2000 Academic Press.

Hydration of non-polar anti-parallel β-sheets

NASA Astrophysics Data System (ADS)

Urbic, Tomaz; Dias, Cristiano L.

2014-04-01

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

Hydration of non-polar anti-parallel β-sheets

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

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

2014-04-28

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

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.

Amino Acid Interaction (INTAA) web server.

PubMed

Galgonek, Jakub; Vymetal, Jirí; Jakubec, David; Vondrášek, Jirí

2017-07-03

Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their identity, properties and binding capabilities. In order to shed light on the energetic side of interactions of amino acids between themselves and with deoxyribonucleotides, we present the Amino Acid Interaction web server (http://bioinfo.uochb.cas.cz/INTAA/). INTAA offers the calculation of the residue Interaction Energy Matrix for any protein structure (deposited in Protein Data Bank or submitted by the user) and a comprehensive analysis of the interfaces in protein-DNA complexes. The Interaction Energy Matrix web application aims to identify key residues within protein structures which contribute significantly to the stability of the protein. The application provides an interactive user interface enhanced by 3D structure viewer for efficient visualization of pairwise and net interaction energies of individual amino acids, side chains and backbones. The protein-DNA interaction analysis part of the web server allows the user to view the relative abundance of various configurations of amino acid-deoxyribonucleotide pairs found at the protein-DNA interface and the interaction energies corresponding to these configurations calculated using a molecular mechanical force field. The effects of the sugar-phosphate moiety and of the dielectric properties of the solvent on the interaction energies can be studied for the various configurations. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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.

A comparative evaluation of rate of space closure after extraction using E-chain and stretched modules in bimaxillary dentoalveolar protrusion cases.

PubMed

Mitra, Rajat; Londhe, S M; Kumar, Prasanna

2011-04-01

Aim of this study was to compare the rate of space closure between E-chain mechanics in one side of upper arch and by elastomeric module with ligature wire on the contralateral side in same patient. Thirty bimaxillary dentoalveolar protrusion cases were taken up for comprehensive fixed orthodontic treatment after extraction of all first premolars to retract both upper and lower anterior teeth. After initial alignment and levelling, alginate impressions were made for upper and lower arches and models constructed. In the upper arch model a vernier caliper was used to measure the extraction space in both sides from middle point of distal surface of canine to the middle most point of mesial surface of second premolar. This is the amount of space present before the onset of retraction mechanics. During space closure procedure two different retracting components were applied in right and left sides of each case. On right side elastic chain (E-chain) applied in both upper and lower arches and on left side elastomeric module with steel ligature (0.010") stretched double its diameter fixed in both arches. Both the mechanisms produced approximately 250-300 g of force as measured by a tension gauge. After onset of retraction mechanism all patients were recalled after every six weeks for three visits. In all these three visits modules and E-chains were changed. In all three visits impression was made, models constructed, and the remaining available space was measured by a vernier caliper up to 0.1 mm level variations. Mean value for total space closure in case of E-chain was 2.777 mm whereas in case of module with ligature wire the value increased to 3.017 mm. Mean value for rate of space closure in case of E-chain was 0.2143 mm, whereas in case of module with ligature wire the value increased to 0.2343 mm with a standard deviation of 0.001104 and 0.001194, respectively. The standard deviation for total space closure was 0.1305 for E-chain and 0.1487 for module with ligature wire. Space closure by elastomeric module with ligature wire is better than the E-chain.

Fine-tuning blend morphology via alkylthio side chain engineering towards high performance non-fullerene polymer solar cells

NASA Astrophysics Data System (ADS)

Li, Ling; Feng, Liuliu; Yuan, Jun; Peng, Hongjian; Zou, Yingping; Li, Yongfang

2018-03-01

Two medium bandgap polymers (ffQx-TS1, ffQx-TS2) were designed and synthesized to investigate the influence of different alkylthio side chain on the morphology and photovoltaic performance of non-fullerene polymer solar cells (PSCs). Both polymers exhibit similar molecular weights and comparable the highest occupied molecular orbital (HOMO) energy level. However, the polymer with straight alkylthio chain delivers a root-mean-square (RMS) of 0.86 nm, which is slightly lower than that with branched chain (1.40 nm). The lower RMS benefits the ohmic contact between the active lay and interface layer, thus enhanced short circuit current (Jsc) (from 13.54 mA cm-1 to 15.25 mA cm-1) could be obtained. Due to the enhancement of Jsc, better power conversion efficiency (PCE) of 7.69% for ffQx-TS2 could be realized. These results indicated that alkylthio side chain engineering is a promising method to improve photovoltaic performance.

The effects of side-chain-induced disorder on the emission spectra and quantum yields of oligothiophene nano-aggregates. A combined experimental and MD-TDDFT study

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

Hong, Jiyun; Jeon, SuKyung; Kim, Janice J.

2014-07-24

Oligomeric thiophenes are commonly-used components in organic electronics and solar cells. These molecules stack and/or aggregate readily under the processing conditions used to form thin films for these applications, significantly altering their optical and charge-transport properties. To determine how these effects depend on the substitution pattern of the thiophene main chains, nano-aggregates of three sexi-thiophene (6T) oligomers having different alkyl substitution patterns were formed using solvent poisoning techniques and studied using steady-state and time-resolved emission spectroscopy. The results indicate the substantial role played by the side-chain substituents in determining the emissive properties of these species. Both the measured spectral changesmore » and their dependence on substitution are well modeled by combined quantum chemistry and molecular dynamics simulations. The simulations connect the side-chain-induced disorder, which determines the favorable chain packing configurations within the aggregates, with their measured electronic spectra.« less

Radiolysis of N-acetyl amino acids as model compounds for radiation degradation of polypeptides

NASA Astrophysics Data System (ADS)

Wayne Garrett, R.; Hill, David J. T.; Ho, Sook-Ying; O'Donnell, James H.; O'Sullivan, Paul W.; Pomery, Peter J.

Radiation chemical yields of (i) the volatile radiolysis products and (ii) the trapped free radicals from the y-radiolysis of the N-acetyl derivatives of glycine, L-valine, L-phenylalanine and L-tyrosine in the polycrystalline state have been determined at room temperature (303 K). Carbon dioxide was found to be the major molecular product for all these compounds with G(CO 2) varying from 0.36 for N-acetyl-L-tyrosine to 8 for N-acetyl-L-valine. There was evidence for some scission of the N-C α bond, indicated by the production of acetamide and the corresponding aliphatic acid, but the determination reaction was found to be of much lesser importance than the decarboxylation reaction. A protective effect of the aromatic ring in N-acetyl-L-phenylalanine and in N-acetyl-L-tyrosine was indicated by the lower yields of volatile products for these compounds. The yields of trapped free radicals were found to vary with the nature of the amino acid side chain, increasing with chain length and chain branching. The radical yields were decreased by incorporation of an aromatic moiety in the side chain, this effect being greater for the tyrosyl side chain than for the phenyl side chain. The G(R·) values showed a good correlation with G(CO 2) indicating that a common reaction may be involved in radical production and carbon dioxide formation.

Toxic isolectins from the mushroom Boletus venenatus.

PubMed

Horibe, Masashi; Kobayashi, Yuka; Dohra, Hideo; Morita, Tatsuya; Murata, Takeomi; Usui, Taichi; Nakamura-Tsuruta, Sachiko; Kamei, Masugu; Hirabayashi, Jun; Matsuura, Masanori; Yamada, Mina; Saikawa, Yoko; Hashimoto, Kimiko; Nakata, Masaya; Kawagishi, Hirokazu

2010-04-01

Ingestion of the toxic mushroom Boletus venenatus causes a severe gastrointestinal syndrome, such as nausea, repetitive vomiting, diarrhea, and stomachache. A family of isolectins (B. venenatus lectins, BVLs) was isolated as the toxic principles from the mushroom by successive 80% ammonium sulfate-precipitation, Super Q anion-exchange chromatography, and TSK-gel G3000SW gel filtration. Although BVLs showed a single band on SDS-PAGE, they were further divided into eight isolectins (BVL-1 to -8) by BioAssist Q anion-exchange chromatography. All the isolectins showed lectin activity and had very similar molecular weights as detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis. Among them, BVL-1 and -3 were further characterized with their complete amino acid sequences of 99 amino acids determined and found to be identical to each other. In the hemagglutination inhibition assay, both proteins failed to bind to any mono- or oligo-saccharides tested and showed the same sugar-binding specificity to glycoproteins. Among the glycoproteins examined, asialo-fetuin was the strongest inhibitor. The sugar-binding specificity of each isolectin was also analyzed by using frontal affinity chromatography and surface plasmon resonance analysis, indicating that they recognized N-linked sugar chains, especially Galbeta1-->4GlcNAcbeta1-->4Manbeta1-->4GlcNAcbeta1-->4GlcNAc (Type II) residues in N-linked sugar chains. BVLs ingestion resulted in fatal toxicity in mice upon intraperitoneal administration and caused diarrhea upon oral administration in rats. Copyright 2009 Elsevier Ltd. All rights reserved.

Ion chromatographic methods for the detection of starch hydrolysis products in ruminal digesta.

PubMed

Barsuhn, K; Kotarski, S F

1991-06-21

Dionex high-performance ion chromatographic methods were evaluated for separation and quantitation of plant sugars and starch digestion products in the ruminal digesta of cattle. Mono- and disaccharides were eluted from a Dionex CarboPac PA1 column with sodium hydroxide used isocratically or as a pH gradient. Maltooligosaccharides which had a degree of polymerization (DP) less than 30 glucose residues were eluted in 60 min by a sodium hydroxide eluent containing a sodium acetate gradient. Carbohydrates were detected amperometrically. Responses were linear (r2 greater than 0.99) for glucose, disaccharides and maltooligosaccharides (DP less than 8). Precipitation and solid-phase extraction methods were evaluated for clean-up of samples of feedstuffs, ruminal contents, and bacterial culture fluids. Perchloric acid precipitation hydrolyzed sucrose but did not affect recoveries of cellobiose, isomaltose or maltose. Ethanol in concentrations of 79 and 86% precipitated maltooligosaccharides having chain lengths larger than 14 and 9 glucose residues, respectively. Maltooligosaccharide recoveries from solid-phase extraction columns varied with maltooligosaccharide size and column packing. Recoveries were greater than 94% for short chains (DP less than 6) eluted from phenyl-substituted columns and variable for all oligosaccharides eluted from C18 columns. Applications of these methods are presented and include: (1) detection of sugars in ruminant feed, (2) monitoring changes in ruminal sugars after feeding and (3) monitoring changes in extracellular sugars and oligosaccharides in the culture fluids of the ruminal bacterium, Bacteroides ruminicola.

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2013-10-01

acids. These sites constitute a variable environment, with the effect of mutations largely isolated to effects on interactions with the P4 side chain. 2...desires to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only...first five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2012-10-14

effect of mutations largely isolated to effects on interactions with the P4 side chain. 2) Most mutations at some sites (e.g. 126, 128) decrease...to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only ground...five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus of the

BetaSCPWeb: side-chain prediction for protein structures using Voronoi diagrams and geometry prioritization.

PubMed

Ryu, Joonghyun; Lee, Mokwon; Cha, Jehyun; Laskowski, Roman A; Ryu, Seong Eon; Kim, Deok-Soo

2016-07-08

Many applications, such as protein design, homology modeling, flexible docking, etc. require the prediction of a protein's optimal side-chain conformations from just its amino acid sequence and backbone structure. Side-chain prediction (SCP) is an NP-hard energy minimization problem. Here, we present BetaSCPWeb which efficiently computes a conformation close to optimal using a geometry-prioritization method based on the Voronoi diagram of spherical atoms. Its outputs are visual, textual and PDB file format. The web server is free and open to all users at http://voronoi.hanyang.ac.kr/betascpweb with no login requirement. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fuel cell catalyst layers containing short-side-chain perfluorosulfonic acid ionomers

NASA Astrophysics Data System (ADS)

Peron, Jennifer; Edwards, Dave; Haldane, Mark; Luo, Xiaoyan; Zhang, Yongming; Holdcroft, Steven; Shi, Zhiqing

Porous catalyst layers (CLs) containing short-side-chain (SSC) perfluorosulfonic acid (PFSA) ionomers of different ion exchange capacity (IEC: 1.3, 1.4 and 1.5 meq g -1) were deposited onto Nafion 211 to form catalyst-coated membranes. The porosity of SSC-PFSA-based CLs is larger than Nafion-CL analogues. CLs incorporating SSC ionomer extend the current density of fuel cell polarization curves at elevated temperature and lower relative humidity compared to those based on long-side chain PFSA (e.g., Nafion)-based CLs. Fuel cell polarization performance was greatly improved at 110 °C and 30% relative humidity (RH) when SSC PFSI was incorporated into the catalyst layer.

Comparative Study of Surface-Active Properties and Antimicrobial Activities of Disaccharide Monoesters

PubMed Central

Zhang, Xi; Song, Fei; Taxipalati, Maierhaba; Wei, Wei; Feng, Fengqin

2014-01-01

The objective of this research was to determine the effect of sugar or fatty acid in sugar ester compounds on the surface-active properties and antimicrobial activities of these compounds. Disaccharides of medium-chain fatty acid monoesters were synthesized through transesterifications by immobilized lipase (Lipozyme TLIM) to yield nine monoesters for subsequent study. Their antimicrobial activities were investigated using three pathogenic microorganisms: Staphylococcus aureus, Escherichia coli O157:H7 and Candida albicans. Their surface-active properties including air–water surface tension, critical micelle concentration, and foaming and emulsion power and stability were also studied. The results showed that all of the tested monoesters were more effective against Staphylococcus aureus (Gram-positive bacterium) than against Escherichia coli O157:H7 (Gram-negative bacterium). The results demonstrated that the carbon chain length was the most important factor influencing the surface properties, whereas degree of esterification and hydrophilic groups showed little effect. PMID:25531369

Substrate scope of a dehydrogenase from Sphingomonas species A1 and its potential application in the synthesis of rare sugars and sugar derivatives.

PubMed

Beer, Barbara; Pick, André; Döring, Manuel; Lommes, Petra; Sieber, Volker

2018-07-01

Rare sugars and sugar derivatives that can be obtained from abundant sugars are of great interest to biochemical and pharmaceutical research. Here, we describe the substrate scope of a short-chain dehydrogenase/reductase from Sphingomonas species A1 (SpsADH) in the oxidation of aldonates and polyols. The resulting products are rare uronic acids and rare sugars respectively. We provide insight into the substrate recognition of SpsADH using kinetic analyses, which show that the configuration of the hydroxyl groups adjacent to the oxidized carbon is crucial for substrate recognition. Furthermore, the specificity is demonstrated by the oxidation of d-sorbitol leading to l-gulose as sole product instead of a mixture of d-glucose and l-gulose. Finally, we applied the enzyme to the synthesis of l-gulose from d-sorbitol in an in vitro system using a NADH oxidase for cofactor recycling. This study shows the usefulness of exploring the substrate scope of enzymes to find new enzymatic reaction pathways from renewable resources to value-added compounds. © 2018 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

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

Chao, Pengjie; Wang, Huan; Mo, Daize

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

Synergistic effects of chlorination and a fully two-dimensional side-chain design on molecular energy level modulation toward non-fullerene photovoltaics

DOE PAGES

Chao, Pengjie; Wang, Huan; Mo, Daize; ...

2017-12-18

By taking the advantage of chlorination and fully conjugated side chains,2D-PBTClshows a PCE of up to 8.81% in non-fullerene solar cells, which corresponds to an approximately 28% improvement compared to that ofPTB7-Th-based devices.

Correction of erroneously packed protein's side chains in the NMR structure based on ab initio chemical shift calculations.

PubMed

Zhu, Tong; Zhang, John Z H; He, Xiao

2014-09-14

In this work, protein side chain (1)H chemical shifts are used as probes to detect and correct side-chain packing errors in protein's NMR structures through structural refinement. By applying the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of chemical shifts, incorrect side chain packing was detected in the NMR structures of the Pin1 WW domain. The NMR structure is then refined by using molecular dynamics simulation and the polarized protein-specific charge (PPC) model. The computationally refined structure of the Pin1 WW domain is in excellent agreement with the corresponding X-ray structure. In particular, the use of the PPC model yields a more accurate structure than that using the standard (nonpolarizable) force field. For comparison, some of the widely used empirical models for chemical shift calculations are unable to correctly describe the relationship between the particular proton chemical shift and protein structures. The AF-QM/MM method can be used as a powerful tool for protein NMR structure validation and structural flaw detection.

Entropy and enthalpy of interaction between amino acid side chains in nanopores

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

Vaitheeswaran, S., E-mail: vaithee05@gmail.com; Thirumalai, D.; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742

2014-12-14

Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientationsmore » between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.« less

Systematic and efficient side chain optimization for molecular docking using a cheapest-path procedure.

PubMed

Schumann, Marcel; Armen, Roger S

2013-05-30

Molecular docking of small-molecules is an important procedure for computer-aided drug design. Modeling receptor side chain flexibility is often important or even crucial, as it allows the receptor to adopt new conformations as induced by ligand binding. However, the accurate and efficient incorporation of receptor side chain flexibility has proven to be a challenge due to the huge computational complexity required to adequately address this problem. Here we describe a new docking approach with a very fast, graph-based optimization algorithm for assignment of the near-optimal set of residue rotamers. We extensively validate our approach using the 40 DUD target benchmarks commonly used to assess virtual screening performance and demonstrate a large improvement using the developed side chain optimization over rigid receptor docking (average ROC AUC of 0.693 vs. 0.623). Compared to numerous benchmarks, the overall performance is better than nearly all other commonly used procedures. Furthermore, we provide a detailed analysis of the level of receptor flexibility observed in docking results for different classes of residues and elucidate potential avenues for further improvement. Copyright © 2013 Wiley Periodicals, Inc.

Effects of Eurycoma longifolia provision on blood sugar level, cholesterols, and uric acid of Etawa Crossbreed Goat

NASA Astrophysics Data System (ADS)

Pratomo, Hurip

2018-05-01

Previous research on male white rat with provision of Eurycoma longifolia until the 3rd days has increased significantly on the formation of final spermatid from spermatozoon, and testosterone, and increase activity of pituitary cell producing the LH hormone. However, these researches yet studied on possibility of side effects caused by provision of Eurycoma longifolia for 6 days on male EC goat. The research aims to measure the effect of Eurycoma longifolia on the levels of: 1). Blood sugar, 2). Cholesterols, and 3). Uric acid of Male Etawa Crossbreed (EC) goat. This research was conducted through two treatment groups, namely : 1). Control group (provision of aquadest) for 1 day, 3 days, and 6 days, 2) Eurycoma longifolia group with a dose of 90 mg/kg body weight (bb) for 1 day, 3 days, and 6 days. Measurements on the sugar blood, cholesterol and uric acid level were conducted in the 1st, 2nd and 6th days. The obtained data were analyzed using Duncan test with confidence level by 95% (α=0,05) comparing the sugar blood, cholesterol and uric acid measured from the control group in the 1st, 3rd and 6th days with the same compound level measured from the Eurycoma longifolia treatment group in the 1st, 3rd and 6th days. The result obtained there were no significant changes on the sugar blood, cholesterol and uric acid levels between all Eurycoma longifolia treatment groups compared to the control group in the 1st, 3rd and 6th days. Thus, the Eurycoma longifolia provision until in the 6th day did not provide any negative side effects and can be applied in the Etawa crossbreed goat farm.

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.

Mapping the Geometric Evolution of Protein Folding Motor.

PubMed

Jerath, Gaurav; Hazam, Prakash Kishore; Shekhar, Shashi; Ramakrishnan, Vibin

2016-01-01

Polypeptide chain has an invariant main-chain and a variant side-chain sequence. How the side-chain sequence determines fold in terms of its chemical constitution has been scrutinized extensively and verified periodically. However, a focussed investigation on the directive effect of side-chain geometry may provide important insights supplementing existing algorithms in mapping the geometrical evolution of protein chains and its structural preferences. Geometrically, folding of protein structure may be envisaged as the evolution of its geometric variables: ϕ, and ψ dihedral angles of polypeptide main-chain directed by χ1, and χ2 of side chain. In this work, protein molecule is metaphorically modelled as a machine with 4 rotors ϕ, ψ, χ1 and χ2, with its evolution to the functional fold is directed by combinations of its rotor directions. We observe that differential rotor motions lead to different secondary structure formations and the combinatorial pattern is unique and consistent for particular secondary structure type. Further, we found that combination of rotor geometries of each amino acid is unique which partly explains how different amino acid sequence combinations have unique structural evolution and functional adaptation. Quantification of these amino acid rotor preferences, resulted in the generation of 3 substitution matrices, which later on plugged in the BLAST tool, for evaluating their efficiency in aligning sequences. We have employed BLOSUM62 and PAM30 as standard for primary evaluation. Generation of substitution matrices is a logical extension of the conceptual framework we attempted to build during the development of this work. Optimization of matrices following the conventional routines and possible application with biologically relevant data sets are beyond the scope of this manuscript, though it is a part of the larger project design.

Zinc Binding and Dimerization of Streptococcus pyogenes Pyrogenic Exotoxin C Are Not Essential for T-Cell Stimulation

DTIC Science & Technology

2003-03-14

streptococcal superantigen binding to MHCII on the surface of cells (7–9), suggesting an essential role in both MHCII molecular recognition and TCR-mediated...extent, mutations of side chains found in a second conserved MHCII alpha-chain-binding site consisting of a hydrophobic surface loop decreased T-cell...fraction of dimer is present at T-cell stimulatory concentrations of Spe-C following mutation of the unpaired side chain of cys- teine at residue 27 to

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.

Decorin inhibits cell migration through a process requiring its glycosaminoglycan side chain.

PubMed

Merle, B; Durussel, L; Delmas, P D; Clézardin, P

1999-12-01

Several studies overwhelmingly support the notion that decorin (DCN) is involved in matrix assembly, and in the control of cell adhesion and proliferation. However, nothing is known about the role of DCN during cell migration. Cell migration is a tightly regulated process which requires both adhesion (at the leading edge of the cell) and de-adhesion (at the trailing edge of the cell) from the substratum. We have determined in this study the effect of DCN on MG-63 osteosarcoma cell migration and have analyzed whether its effect is mediated by the protein core and/or the glycosaminoglycan side chain. DCN impeded the migration-promoting effect of matrix molecules (fibronectin, collagen type I) known to interact with the proteoglycan. Conversely, DCN did not counteract the migration-promoting effect of fibrinogen lacking proteoglycan affinity. DCN bearing dermatan-sulfate chains (i.e., skin and cartilage DCN) was about 20-fold more effective in inhibiting cell migration than DCN bearing chondroitin-sulfate chains (i.e., bone DCN). In addition, chondroitinase AC-treatment of cartilage DCN (which specifically removes chondroitin-sulfate chains) did not attenuate the inhibitory effect of this proteoglycan, while cartilage DCN deprived of both chondroitin- and dermatan-sulfate chains failed to alter cell migration promoted by either fibronectin or its heparin- and cell-binding domains. These data assert that the dermatan-sulfate chains of DCN are responsible for a negative influence on cell migration. However, isolated glycosaminoglycans failed to alter cell migration promoted by fibronectin, indicating that strongly negatively charged glycosaminoglycans alone cannot account for the impaired cell motility seen with DCN. Overall, these results show that the inhibitory action of DCN is dependent of substratum binding, is differentially mediated by its glycosaminoglycan side chains (chondroitin-sulfate vs. dermatan-sulfate chains), and is independent of a steric hindrance effect exerted by its glycosaminoglycan side chains. Copyright 1999 Wiley-Liss, Inc.

Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the high-density lipoprotein receptor SR-BI.

PubMed

Yu, Miao; Lau, Thomas Y; Carr, Steven A; Krieger, Monty

2012-12-18

The high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys(321)-Pro(322)-Cys(323) (CPC) motif and connect Cys(280) to Cys(334). We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys(384) to HDL binding and lipid uptake. The effects of CPC mutations on activity were context-dependent. Full wild-type (WT) activity required Pro(322) and Cys(323) only when Cys(321) was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX, or XXX mutants (X ≠ WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys(323) is deleterious, perhaps because of aberrant disulfide bond formation. Pro(322) may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for normal activity. C(384)X (X = S, T, L, Y, G, or A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (enhanced binding, weakened uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C(384)X mutants were BLT-1-resistant, supporting the proposal that Cys(384)'s thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories.

Single-Point Mutation with a Rotamer Library Toolkit: Toward Protein Engineering.

PubMed

Pottel, Joshua; Moitessier, Nicolas

2015-12-28

Protein engineers have long been hard at work to harness biocatalysts as a natural source of regio-, stereo-, and chemoselectivity in order to carry out chemistry (reactions and/or substrates) not previously achieved with these enzymes. The extreme labor demands and exponential number of mutation combinations have induced computational advances in this domain. The first step in our virtual approach is to predict the correct conformations upon mutation of residues (i.e., rebuilding side chains). For this purpose, we opted for a combination of molecular mechanics and statistical data. In this work, we have developed automated computational tools to extract protein structural information and created conformational libraries for each amino acid dependent on a variable number of parameters (e.g., resolution, flexibility, secondary structure). We have also developed the necessary tool to apply the mutation and optimize the conformation accordingly. For side-chain conformation prediction, we obtained overall average root-mean-square deviations (RMSDs) of 0.91 and 1.01 Å for the 18 flexible natural amino acids within two distinct sets of over 3000 and 1500 side-chain residues, respectively. The commonly used dihedral angle differences were also evaluated and performed worse than the state of the art. These two metrics are also compared. Furthermore, we generated a family-specific library for kinases that produced an average 2% lower RMSD upon side-chain reconstruction and a residue-specific library that yielded a 17% improvement. Ultimately, since our protein engineering outlook involves using our docking software, Fitted/Impacts, we applied our mutation protocol to a benchmarked data set for self- and cross-docking. Our side-chain reconstruction does not hinder our docking software, demonstrating differences in pose prediction accuracy of approximately 2% (RMSD cutoff metric) for a set of over 200 protein/ligand structures. Similarly, when docking to a set of over 100 kinases, side-chain reconstruction (using both general and biased conformation libraries) had minimal detriment to the docking accuracy.

Evaluating Force Fields for the Computational Prediction of Ionized Arginine and Lysine Side-Chains Partitioning into Lipid Bilayers and Octanol.

PubMed

Sun, Delin; Forsman, Jan; Woodward, Clifford E

2015-04-14

Abundant peptides and proteins containing arginine (Arg) and lysine (Lys) amino acids can apparently permeate cell membranes with ease. However, the mechanisms by which these peptides and proteins succeed in traversing the free energy barrier imposed by cell membranes remain largely unestablished. Precise thermodynamic studies (both theoretical and experimental) on the interactions of Arg and Lys residues with model lipid bilayers can provide valuable clues to the efficacy of these cationic peptides and proteins. We have carried out molecular dynamics simulations to calculate the interactions of ionized Arg and Lys side-chains with the zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer for 10 widely used lipid/protein force fields: CHARMM36/CHARMM36, SLIPID/AMBER99SB-ILDN, OPLS-AA/OPLS-AA, Berger/OPLS-AA, Berger/GROMOS87, Berger/GROMOS53A6, GROMOS53A6/GROMOS53A6, nonpolarizable MARTINI, polarizable MARTINI, and BMW MARTINI. We performed umbrella sampling simulations to obtain the potential of mean force for Arg and Lys side-chains partitioning from water to the bilayer interior. We found significant differences between the force fields, both for the interactions between side-chains and bilayer surface, as well as the free energy cost for placing the side-chain at the center of the bilayer. These simulation results were compared with the Wimley-White interfacial scale. We also calculated the free energy cost for transferring ionized Arg and Lys side-chains from water to both dry and wet octanol. Our simulations reveal rapid diffusion of water molecules into octanol whereby the equilibrium mole fraction of water in the wet octanol phase was ∼25%. Surprisingly, our free energy calculations found that the high water content in wet octanol lowered the water-to-octanol partitioning free energies for cationic residues by only 0.6 to 0.7 kcal/mol.

Structures and application of oligosaccharides in human milk.

PubMed

Kobata, Akira

2010-01-01

Comparative study of the oligosaccharide profiles of individual human milk revealed the presence of three different patterns. Four oligosaccharides containing the Fucalpha1-2Gal group were missing in the milk of non-secretor, and three oligosaccharides containing the Fucalpha1-4GlcNAc group were missing in the milk of Lewis negative individuals. Disappearance of some major oligosaccharides in these samples led to the finding of five novel minor oligosaccharides, which were hidden under the missing oligosaccharides. Following these studies, structures of many novel milk oligosaccharides were elucidated. At least 13 core oligosaccharides were found in these oligosaccharides. By adding alpha-fucosyl residues and sialic acid residues to these core oligosaccharides, more than one hundred oligosaccharides were formed. All these oligosaccharides contain lactose at their reducing termini. This evidence, together with the deletion phenomena found in the milk oligosaccharides of non-secretor and Lewis negative individuals, suggested that the oligosaccharides are formed from lactose by the concerted action of glycosyltransferases, which are responsible for elongation and branching of the Galbeta1-4GlcNAc group in the sugar chains of glycoconjugates on the surface of epithelial cells. Therefore, oligosaccharides in human milk could include many structures, starting from the Galbeta1-4GlcNAc group in the sugar chains of various glycoconjugates. Many lines of evidence recently indicated that virulent enteric bacteria and viruses start their infection by binding to particular sugar chains of glycoconjugates on the target cell surfaces. Therefore, milk oligosaccharides could be useful for developing drugs, which inhibit the infection of bacteria and viruses.

Structure–Function Studies of Hydrophobic Residues That Clamp a Basic Glutamate Side Chain during Catalysis by Triosephosphate Isomerase

PubMed Central

2016-01-01

Kinetic parameters are reported for the reactions of whole substrates (kcat/Km, M–1 s–1) (R)-glyceraldehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) and for the substrate pieces [(kcat/Km)E·HPi/Kd, M–2 s–1] glycolaldehyde (GA) and phosphite dianion (HPi) catalyzed by the I172A/L232A mutant of triosephosphate isomerase from Trypanosoma brucei brucei (TbbTIM). A comparison with the corresponding parameters for wild-type, I172A, and L232A TbbTIM-catalyzed reactions shows that the effect of I172A and L232A mutations on ΔG⧧ for the wild-type TbbTIM-catalyzed reactions of the substrate pieces is nearly the same as the effect of the same mutations on TbbTIM previously mutated at the second side chain. This provides strong evidence that mutation of the first hydrophobic side chain does not affect the functioning of the second side chain in catalysis of the reactions of the substrate pieces. By contrast, the effects of I172A and L232A mutations on ΔG⧧ for wild-type TbbTIM-catalyzed reactions of the whole substrate are different from the effect of the same mutations on TbbTIM previously mutated at the second side chain. This is due to the change in the rate-determining step that determines the barrier to the isomerization reaction. X-ray crystal structures are reported for I172A, L232A, and I172A/L232A TIMs and for the complexes of these mutants to the intermediate analogue phosphoglycolate (PGA). The structures of the PGA complexes with wild-type and mutant enzymes are nearly superimposable, except that the space opened by replacement of the hydrophobic side chain is occupied by a water molecule that lies ∼3.5 Å from the basic side chain of Glu167. The new water at I172A mutant TbbTIM provides a simple rationalization for the increase in the activation barrier ΔG⧧ observed for mutant enzyme-catalyzed reactions of the whole substrate and substrate pieces. By contrast, the new water at the L232A mutant does not predict the decrease in ΔG⧧ observed for the mutant enzyme-catalyzed reactions of the substrate piece GA. PMID:27149328

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

PubMed

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

2016-03-31

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

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

NASA Astrophysics Data System (ADS)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng pectin on galectin-3 and its structure-activity relationship.

PubMed

Gao, Xiaoge; Zhi, Yuan; Sun, Lin; Peng, Xiaoxia; Zhang, Tao; Xue, Huiting; Tai, Guihua; Zhou, Yifa

2013-11-22

Pectin has been shown to inhibit the actions of galectin-3, a β-galactoside-binding protein associated with cancer progression. The structural features of pectin involved in this activity remain unclear. We investigated the effects of different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination, cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T-cells. RG-I-4 specifically bound to the carbohydrate recognition domain of galectin-3 with a dissociation constant of 22.2 nm, which was determined by surface plasmon resonance analysis. The structure-activity relationship of RG-I-4 was investigated by modifying the structure through various enzymatic and chemical methods followed by activity tests. The results showed that (a) galactan side chains were essential to the activity of RG-I-4, whereas arabinan side chains positively or negatively regulated the activity depending on their location within the RG-I-4 molecule. (b) The activity of galactan chain was proportional to its length up to 4 Gal residues and largely unchanged thereafter. (c) The majority of galactan side chains in RG-I-4 were short with low activities. (d) The high activity of RG-I-4 resulted from the cooperative action of these side chains. (e) The backbone of the molecule was very important to RG-I-4 activity, possibly by maintaining a structural conformation of the whole molecule. (f) The isolated backbone could bind galectin-3, which was insensitive to lactose treatment. The novel discovery that the side chains and backbone play distinct roles in regulating RG-I-4 activity is valuable for producing highly active pectin-based galectin-3 inhibitors.

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

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

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

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

2014-03-20

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

Exploration of Structural Changes in Lactose Permease on Sugar Binding and Proton Transport through Atomistic Simulations

NASA Astrophysics Data System (ADS)

Liu, Jin; Jewel, Yead; Dutta, Prashanta

2017-11-01

Escherichia coli lactose permease (LacY) actively transports lactose and other galactosides across cell membranes through lactose/H+ symport process. Lactose/H+ symport is a highly complex process that involves large-scale protein conformational changes. The complete picture of lactose/H+ symport is largely unclear. In this work, we develop the force field for sugar molecules compatible with PACE, a hybrid and coarse-grained force field that couples the united-atom protein models with the coarse-grained MARTINI water/lipid. After validation, we implement the new force field to investigate the binding of a β-D-galactopyranosyl-1-thio- β-D-galactopyranoside (TDG) molecule to a wild-type LacY. Transitions from inward-facing to outward-facing conformations upon TDG binding and protonation of Glu269 have been achieved from microsecond simulations. Both the opening of the periplasmic side and closure of the cytoplasmic side of LacY are consistent with experiments. Our analysis suggest that the conformational changes of LacY are a cumulative consequence of inter-domain H-bonds breaking at the periplasmic side, inter-domain salt-bridge formation at the cytoplasmic side, as well as the TDG orientational changes during the transition. This work is supported by US National Science Foundation under Grant No. CBET-1604211.

Characterization of Lipid A Variants by Energy-Resolved Mass Spectrometry: Impact of Acyl Chains

NASA Astrophysics Data System (ADS)

Crittenden, Christopher M.; Akin, Lucas D.; Morrison, Lindsay J.; Trent, M. Stephen; Brodbelt, Jennifer S.

2017-06-01

Lipid A molecules consist of a diglucosamine sugar core with a number of appended acyl chains that vary in their length and connectivity. Because of the challenging nature of characterizing these molecules and differentiating between isomeric species, an energy-resolved MS/MS strategy was undertaken to track the fragmentation trends and map genealogies of product ions originating from consecutive cleavages of acyl chains. Generalizations were developed based on the number and locations of the primary and secondary acyl chains as well as variations in preferential cleavages arising from the location of the phosphate groups. Secondary acyl chain cleavage occurs most readily for lipid A species at the 3' position, followed by primary acyl chain fragmentation at both the 3' and 3 positions. In the instances of bisphosphorylated lipid A variants, phosphate loss occurs readily in conjunction with the most favorable primary and secondary acyl chain cleavages. [Figure not available: see fulltext.

7 CFR 1435.501 - Bid submission procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... those years that they were fully operational); (v) The value of CCC sugar to be received as payment; and... the balance. (3) Contiguous areas of land must have a minimum width of 3 chains (198 feet). (e) For a...

Carbohydrate binding specificity of pea lectin studied by NMR spectroscopy and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Cheong, Youngjoo; Shim, Gyuchang; Kang, Dongil; Kim, Yangmee

1999-02-01

The conformational details of Man( α1,6)Man( α)OMe are investigated through NMR spectroscopy in conjunction with molecular modeling. The lowest energy structure (M1) in the adiabatic energy map calculated with a dielectric constant of 50 has glycosidic dihedral angles of φ=-60°, ψ=180° and ω=180°. The other low energy structure (M2) has glycosidic dihedral angles of φ=-60°, ψ=180° and ω=-60°. Molecular dynamics simulations and NMR experiments prove that Man( α1,6)Man( α)OMe in the free form exists with conformational averaging of M1 and M2 conformers predominantly. Molecular dynamics simulations of the pea lectin-carbohydrate complex with explicit water molecules starting from the X-ray crystallographic structure of pea lectin show that the protein-carbohydrate interaction centers mainly on the hydrogen bonds and van der Waals interactions between protein and carbohydrate. From the molecular dynamics simulation, it is found that the M1 structure can bind to pea lectin better than the M2 structure. The origin of this selectivity is the water- mediated hydrogen bond interactions between the remote mannose and the binding site of pea lectin as well as the direct hydrogen bond interaction between the terminal mannose and pea lectin. Extensive networks of interactions in the carbohydrate binding site and the metal binding site are important in maintaining the carbohydrate binding properties of pea lectin. Especially, the predominant factors of mannose binding specificity of pea lectin are the hydrogen bond interactions between the 4th hydroxyl groups of the terminal sugar ring and the side chains of Asp-81 and Asn-125 in the carbohydrate binding site, and the additional interactions between these side chains of Asp-81 and Asn-125 and the calcium ion in the metal binding site of pea lectin.

Adaptation of an L-proline adenylation domain to use 4-propyl-L-proline in the evolution of lincosamide biosynthesis.

PubMed

Kadlčík, Stanislav; Kučera, Tomáš; Chalupská, Dominika; Gažák, Radek; Koběrská, Markéta; Ulanová, Dana; Kopecký, Jan; Kutejová, Eva; Najmanová, Lucie; Janata, Jiří

2013-01-01

Clinically used lincosamide antibiotic lincomycin incorporates in its structure 4-propyl-L-proline (PPL), an unusual amino acid, while celesticetin, a less efficient related compound, makes use of proteinogenic L-proline. Biochemical characterization, as well as phylogenetic analysis and homology modelling combined with the molecular dynamics simulation were employed for complex comparative analysis of the orthologous protein pair LmbC and CcbC from the biosynthesis of lincomycin and celesticetin, respectively. The analysis proved the compared proteins to be the stand-alone adenylation domains strictly preferring their own natural substrate, PPL or L-proline. The LmbC substrate binding pocket is adapted to accommodate a rare PPL precursor. When compared with L-proline specific ones, several large amino acid residues were replaced by smaller ones opening a channel which allowed the alkyl side chain of PPL to be accommodated. One of the most important differences, that of the residue corresponding to V306 in CcbC changing to G308 in LmbC, was investigated in vitro and in silico. Moreover, the substrate binding pocket rearrangement also allowed LmbC to effectively adenylate 4-butyl-L-proline and 4-pentyl-L-proline, substrates with even longer alkyl side chains, producing more potent lincosamides. A shift of LmbC substrate specificity appears to be an integral part of biosynthetic pathway adaptation to the PPL acquisition. A set of genes presumably coding for the PPL biosynthesis is present in the lincomycin--but not in the celesticetin cluster; their homologs are found in biosynthetic clusters of some pyrrolobenzodiazepines (PBD) and hormaomycin. Whereas in the PBD and hormaomycin pathways the arising precursors are condensed to another amino acid moiety, the LmbC protein is the first functionally proved part of a unique condensation enzyme connecting PPL to the specialized amino sugar building unit.

Blood Pressure Regulation: Reviewing Evidence for Interplay Between Common Dietary Sugars and Table Salt.

PubMed

Preuss, Harry G; Clouatre, Dallas; Swaroop, Anand; Bagchi, Manashi; Bagchi, Debasis; Kaats, Gilbert R

2017-01-01

A popular concept is that the significant global progression in prevalence and intensification of elevated blood pressure (BP) levels is due in part to dietary indiscretions. Excess intake of several food sources causing overweight/obesity plays an important role in BP perturbations. However, certain nutrients are involved in ways other than via body fat accumulation, particularly table salt (sodium chloride) and popular refined carbohydrates like dietary sugars (sucrose, fructose, high fructose corn syrup). In nondiabetics and diabetics, several functions of salt and sugar influence BP and metabolism. For example, salt intake is linked to volume expansion, insulin resistance, and hypertension, while sugar intake is associated with enhanced salt sensitivity via urinary sodium retention, insulin resistance, and hypertension. The key postulate evaluated here is that when two popular nutrients-salt and dietary sugars-are consumed together in adequate amounts, their respective individual BP effects are significantly amplified. In previous laboratory studies, a sugar challenge did not increase BP in the face of marked sodium depletion, and combining sugar and salt challenges caused a synergistic BP elevation. Among examples of amplification on the clinical side, the greatest increases in BP following sugar challenges were seen in diabetic subjects having the highest sodium excretion. Interplay between table salt and common dietary sugars in BP regulation is a reasonable postulate and should be carefully considered when developing optimal prevention and treatment regimens to ameliorate the worldwide crisis arising from harmful elevated BP levels.

[Sugar of substitute stevioside in chewing gum: comparative double blind controllable study].

PubMed

Rumiantsev, V A; Beliaev, V V; Zubtsov, V A; Esaian, L K; Namestnikova, I V

2011-01-01

In double blind controllable study on 126 volunteers - students of medical academy - influence on рН the mixed saliva of 5 kinds of chewing gums with the different contents of substitute of sugar as xylitol and sorbitol, and also the chewing sweets R.O.C.S., two kinds of chewing gums containing a basis with substitute of sugar stevioside (1.25 and 2.5%) and placebo (a basis without additives) were investigated. Products chewed within 10 minutes. In one of groups surveyed such chewing was preceded with rinsing a mouth by a test solution of saccharose. рН determined within 30 minutes. At chewing gums with substitute of sugar displacement рН the mixed saliva in the alkaline side was revealed a different degree. Thus gums with stevioside did not concede and even surpassed in this action of chewing gums with other substitutes of sugar. In comparison with placebo chewing gums and sweets restored acid-alkaline balance of oral cavities faster. Hence, use of stevioside in structure of chewing gum allows at preservation of its positive actions in oral cavity essentially to reduce concentration substitute of sugar and, hence, its collateral action by an organism.

Biopolymers Containing Unnatural Amino Acids

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

Schultz, Peter

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

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

PubMed

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

2012-09-15

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

Biopolymers Containing Unnatural Building Blocks

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

Schultz, Peter G.

2013-06-30

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

Compounds having aromatic rings and side-chain amide-functionality and a method for transporting monovalent anions across biological membranes using the same

DOEpatents

Davis, Jeffery T [College Park, MD; Sidorov, Vladimir [Richmond, VA; Kotch, Frank W [New Phila., PA

2008-04-08

A compound containing at least two aromatic rings covalently bonded together, with each aromatic ring containing at least one oxyacetamide-based side chain, the compound being capable of forming a chloride ion channel across a lipid bilayer, and transporting chloride ion across the lipid bilayer.

Novel Semiconducting Polymers for Highly Efficient Solar Energy Harvesting

DTIC Science & Technology

2014-03-11

pyrrole -4,6-dione, a well known electron-deficient monomer, to obtain the new copolymer PTTATPD-1 for comparison in physical properties. The number...bulk side chain showed a PCE about 0.6%; PTTATT-4 with 2- ethyldedocyl side chain showed a PCE about 3.0% and the copolymer with thieno[3,4-c] pyrrol

Polymer non-fullerene solar cells of vastly different efficiencies for minor side-chain modification: impact of charge transfer, carrier lifetime, morphology and mobility

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

Awartani, Omar M.; Gautam, Bhoj; Zhao, Wenchao

The performance of the 11.25% efficient PBDB-T : ITIC system degraded to 4.35% after a minor side-chain modification in PBDB-O : ITIC. In this study, the underlying reasons behind this vast difference in efficiencies are investigated.

Ring structure modifications of phenylalanine 19 increase fibrillation kinetics and reduce toxicity of amyloid β (1-40).

PubMed

Korn, Alexander; Surendran, Dayana; Krueger, Martin; Maiti, Sudipta; Huster, Daniel

2018-05-24

We investigated the influence of the chemical structure of the phenylalanine side chain in position 19 of the 40 residue amyloid β peptide. Side chain modifications in this position yielded fibrils of essentially unaltered morphology, structure, and dynamics, but significantly increased fibrillation kinetics and diminished the toxicity of the peptides.

Side-chain Liquid Crystal Polymers (SCLCP): Methods and Materials. An Overview

PubMed Central

Ganicz, Tomasz; Stańczyk, Włodzimierz

2009-01-01

This review focuses on recent developments in the chemistry of side chain liquid crystal polymers. It concentrates on current trends in synthetic methods and novel, well defined structures, supramolecular arrangements, properties, and applications. The review covers literature published in this century, apart from some areas, such as dendritic and elastomeric systems, which have been recently reviewed.

Polymer non-fullerene solar cells of vastly different efficiencies for minor side-chain modification: impact of charge transfer, carrier lifetime, morphology and mobility

DOE PAGES

Awartani, Omar M.; Gautam, Bhoj; Zhao, Wenchao; ...

2018-01-01

The performance of the 11.25% efficient PBDB-T : ITIC system degraded to 4.35% after a minor side-chain modification in PBDB-O : ITIC. In this study, the underlying reasons behind this vast difference in efficiencies are investigated.

Solvent polarity effects on supramolecular chirality of a polyfluorene-thiophene copolymer.

PubMed

Hirahara, Takashi; Yoshizawa-Fujita, Masahiro; Takeoka, Yuko; Rikukawa, Masahiro

2018-06-01

This study demonstrates the supramolecular chirality control of a conjugated polymer via solvent polarity. We designed and synthesized a chiral polyfluorene-thiophene copolymer having two different chiral side chains at the 9-position of the fluorene unit. Chiral cyclic and alkyl ethers with different polarities were selected as the chiral side chains. The sign of the circular dichroism spectra in the visible wavelength region was affected by the solvent system, resulting from the change of supramolecular structure. The estimation of the solubility parameter revealed that the solubility difference of the side chains contributed to the change of the circular dichroism sign, which was also observed in spin-coated films prepared from good solvents having different polarities. © 2018 Wiley Periodicals, Inc.

A comparative study of mucilage and pulp polysaccharides from tamarillo fruit (Solanum betaceum Cav.).

PubMed

do Nascimento, Georgia Erdmann; Iacomini, Marcello; Cordeiro, Lucimara M C

2016-07-01

A comparative study of mucilage (locular tissue) and pulp polysaccharides from ripe tamarillo fruits (Solanum betaceum Cav.) was carried out. After aqueous and alkaline extractions and various purification steps (freeze-thaw and α-amylase - EC 3.2.1.1 treatments, Fehling precipitation and ultrafiltration through 50 kDa cut-off membrane), the obtained fractions from mucilage were analyzed by sugar composition, HPSEC, and NMR spectroscopy analyses. The results showed that the mucilage of tamarillo contains a highly methoxylated homogalacturonans mixed with type I arabinogalactans, a linear (1 → 5)-linked α-L-arabinan, and a linear (1 → 4)-β-D-xylan. A comparison with polysaccharides extracted from the pulp revealed that differences were observed in the yield and in the ratio of extracted polysaccharides. Moreover, structural differences between pulp and mucilage polysaccharides were also observed, such as in the length of side chains of the pectins, and in the degree of branching of the xylans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Triterpenoids with Promoting Effects on the Differentiation of PC12 Cells from the Steamed Roots of Panax notoginseng.

PubMed

Gu, Cheng-Zhen; Lv, Jun-Jiang; Zhang, Xiao-Xia; Qiao, Yi-Jun; Yan, Hui; Li, Yan; Wang, Dong; Zhu, Hong-Tao; Luo, Huai-Rong; Yang, Chong-Ren; Xu, Min; Zhang, Ying-Jun

2015-08-28

The roots of Panax notoginseng, an important Chinese medicinal plant, have been used traditionally in both the raw and processed forms, due to the different chemical constituents and bioactivities found. Thirty-eight dammarane-type triterpenoid saponins were isolated from the steam-processed roots of P. notoginseng, including 18 new substances, namely, notoginsenosides SP1-SP18 (1-18). The structures of 1-18 were determined on the basis of spectroscopic analysis and acidic hydrolysis. The absolute configuration of the hydroxy group at C-24 in 1-4, 19, and 20 was determined in each case by Mo2(AcO)4-induced circular dichroism. The new compounds were found to feature a diversity of highly oxygenated side chains, formed by hydrolysis of the C-20 sugar moiety followed by dehydration, dehydrogenation, epoxidation, hydroxylation, or methoxylation of the main saponins in the raw roots. The new saponins 1, 2, 6-8, 14, and 17 and the known compounds 20-27 showed promoting effects on the differentiation of PC12 cells, at a concentration of 10 μM.

Structure of a shear-thickening polysaccharide extracted from the New Zealand black tree fern, Cyathea medullaris.

PubMed

Wee, May S M; Matia-Merino, Lara; Carnachan, Susan M; Sims, Ian M; Goh, Kelvin K T

2014-09-01

A shear-thickening water-soluble polysaccharide was purified from mucilage extracted from the fronds of the New Zealand black tree fern (Cyathea medullaris or 'mamaku' in Māori) and its structure characterised. Constituent sugar analysis by three complementary methods, combined with linkage analysis (of carboxyl reduced samples) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR) revealed a glucuronomannan comprising a backbone of 4-linked methylesterified glucopyranosyl uronic acid and 2-linked mannopyranosyl residues, branched at O-3 of 45% and at both O-3 and O-4 of 53% of the mannopyranosyl residues with side chains likely comprising terminal xylopyranosyl, terminal galactopyranosyl, non-methylesterified terminal glucopyranosyl uronic acid and 3-linked glucopyranosyl uronic acid residues. The weight-average molecular weight of the purified polysaccharide was ∼1.9×10(6) Da as determined by size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS). The distinctive rheological properties of this polysaccharide are discussed in relation to its structure. Copyright © 2014 Elsevier B.V. All rights reserved.

Compositional changes in 'Bartlett' pear ( Pyrus communis L.) cell wall polysaccharides as affected by sunlight conditions.

PubMed

Raffo, María D; Ponce, Nora M A; Sozzi, Gabriel O; Vicente, Ariel R; Stortz, Carlos A

2011-11-23

Preharvest conditions can have a great impact on fruit quality attributes and postharvest responses. Firmness is an important quality attribute in pear, and excessive softening increases susceptibility to bruising and decay, thus limiting fruit postharvest life. Textural characteristics of fruits are determined at least in part by cell wall structure and disassembly. Few studies have analyzed the influence of fruit preharvest environment in softening, cell wall composition, and degradation. In the current work 'Bartlett' pears grown either facing the sun (S) or in the shade (H) were harvested and stored for 13 days at 20 °C. An evaluation of fruit soluble solids, acidity, color, starch degradation, firmness, cell wall yield, pectin and matrix glycan solubilization, depolymerization, and monosaccharide composition was carried out. Sun-exposed pears showed more advanced color development and similar levels of starch degradation, sugars, and acids than shaded fruit. Sunlight-grown pears were at harvest firmer than shade-grown pears. Both fruit groups softened during storage at 20 °C, but even after ripening, sun-exposed pears remained firmer. Sunlight exposure did not have a great impact on pectin molecular weight. Instead, at harvest a higher proportion of water-solubilized uronic acids and alkali-solubilized neutral sugars and a larger mean molecular size of tightly bound glycans was found in sun-exposed pears. During ripening cell wall catabolism took place in both sun- and shade-grown pears, but pectin solubilization was clearly delayed in sun-exposed fruit. This was associated with decreased removal of RG I-arabinan side chains rather than with reduced depolymerization.

Sweet proteins – Potential replacement for artificial low calorie sweeteners

PubMed Central

Kant, Ravi

2005-01-01

Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with development of bladder cancer. Naturally occurring sweet and taste modifying proteins are being seen as potential replacements for the currently available artificial low calorie sweeteners. Interaction aspects of sweet proteins and the human sweet taste receptor are being investigated. PMID:15703077

Adsorption of sugar surfactants at the air/water interface.

PubMed

Varga, Imre; Mészáros, Róbert; Stubenrauch, Cosima; Gilányi, Tibor

2012-08-01

The adsorption isotherms of n-decyl-β-D-glucoside (β-C(10)G(1)) as well as various n-alkyl-β-D-maltosides (β-C(n)G(2)) with n=8, 10, 12 and 14 were determined from surface tension measurements. Based on the analysis of the adsorption isotherms, the total free energy change of adsorption was determined and a novel method was proposed to determine the maximum adsorbed amount of surfactant. It can be concluded that the driving force for adsorption first increases with increasing adsorbed amount of the sugar surfactants and then levels off in a plateau. This peculiar behaviour is interpreted as formation of a thin liquid-like alkane film of overlapping alkyl chains at the air/water interface once a certain adsorbed amount is exceeded. The driving force of adsorption depends on the alkyl chain length only and is not affected by the type of the head group. The hydrophobic contribution to the standard free energy change of adsorption was compared with the values of sodium alkylsulfate and alkyltrimethylammonium bromide surfactants. This comparison reveals that the hydrophobic driving force of adsorption is the largest for the sodium alkylsulfates, whereas it is the same for the sugar surfactants and the alkyltrimethylammonium bromides. Copyright © 2012 Elsevier Inc. All rights reserved.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

PubMed

Murphy, P A; Cebula, T A; Windle, B E

1981-10-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

PubMed Central

Murphy, P A; Cebula, T A; Windle, B E

1981-01-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause. PMID:6271680

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.

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.

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.

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.

Prebiotic Synthesis of Autocatalytic Products From Formaldehyde-Derived Sugars as the Carbon and Energy Source

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

2003-01-01

Our research objective is to understand and model the chemical processes on the primitive Earth that generated the first autocatalytic molecules and microstructures involved in the origin of life. Our approach involves: (a) investigation of a model origin-of-life process named the Sugar Model that is based on the reaction of formaldehyde- derived sugars (trioses and tetroses) with ammonia, and (b) elucidation of the constraints imposed on the chemistry of the origin of life by the fixed energies and rates of C,H,O-organic reactions under mild aqueous conditions. Recently, we demonstrated that under mild aqueous conditions the Sugar Model process yields autocatalytic products, and generates organic micropherules (2-20 micron dia.) that exhibit budding, size uniformity, and chain formation. We also discovered that the sugar substrates of the Sugar Model are capable of reducing nitrite to ammonia under mild aqueous conditions. In addition studies done in collaboration with Sandra Pizzarrello (Arizona State University) revealed that chiral amino acids (including meteoritic isovaline) catalyze both the synthesis and specific handedness of chiral sugars. Our systematic survey of the energies and rates of reactions of C,H,O-organic substrates under mild aqueous conditions revealed several general principles (rules) that govern the direction and rate of organic reactions. These reactivity principles constrain the structure of chemical pathways used in the origin of life, and in modern and primitive metabolism.

Glycolipid acquisition by human glycolipid transfer protein dramatically alters intrinsic tryptophan fluorescence: insights into glycolipid binding affinity.

PubMed

Zhai, Xiuhong; Malakhova, Margarita L; Pike, Helen M; Benson, Linda M; Bergen, H Robert; Sugár, István P; Malinina, Lucy; Patel, Dinshaw J; Brown, Rhoderick E

2009-05-15

Glycolipid transfer proteins (GLTPs) are small, soluble proteins that selectively accelerate the intermembrane transfer of glycolipids. The GLTP fold is conformationally unique among lipid binding/transfer proteins and serves as the prototype and founding member of the new GLTP superfamily. In the present study, changes in human GLTP tryptophan fluorescence, induced by membrane vesicles containing glycolipid, are shown to reflect glycolipid binding when vesicle concentrations are low. Characterization of the glycolipid-induced "signature response," i.e. approximately 40% decrease in Trp intensity and approximately 12-nm blue shift in emission wavelength maximum, involved various modes of glycolipid presentation, i.e. microinjection/dilution of lipid-ethanol solutions or phosphatidylcholine vesicles, prepared by sonication or extrusion and containing embedded glycolipids. High resolution x-ray structures of apo- and holo-GLTP indicate that major conformational alterations are not responsible for the glycolipid-induced GLTP signature response. Instead, glycolipid binding alters the local environment of Trp-96, which accounts for approximately 70% of total emission intensity of three Trp residues in GLTP and provides a stacking platform that aids formation of a hydrogen bond network with the ceramide-linked sugar of the glycolipid headgroup. The changes in Trp signal were used to quantitatively assess human GLTP binding affinity for various lipids including glycolipids containing different sugar headgroups and homogenous acyl chains. The presence of the glycolipid acyl chain and at least one sugar were essential for achieving a low-to-submicromolar dissociation constant that was only slightly altered by increased sugar headgroup complexity.

Glycolipid Acquisition by Human Glycolipid Transfer Protein Dramatically Alters Intrinsic Tryptophan Fluorescence

PubMed Central

Zhai, Xiuhong; Malakhova, Margarita L.; Pike, Helen M.; Benson, Linda M.; Bergen, H. Robert; Sugár, István P.; Malinina, Lucy; Patel, Dinshaw J.; Brown, Rhoderick E.

2009-01-01

Glycolipid transfer proteins (GLTPs) are small, soluble proteins that selectively accelerate the intermembrane transfer of glycolipids. The GLTP fold is conformationally unique among lipid binding/transfer proteins and serves as the prototype and founding member of the new GLTP superfamily. In the present study, changes in human GLTP tryptophan fluorescence, induced by membrane vesicles containing glycolipid, are shown to reflect glycolipid binding when vesicle concentrations are low. Characterization of the glycolipid-induced “signature response,” i.e. ∼40% decrease in Trp intensity and ∼12-nm blue shift in emission wavelength maximum, involved various modes of glycolipid presentation, i.e. microinjection/dilution of lipid-ethanol solutions or phosphatidylcholine vesicles, prepared by sonication or extrusion and containing embedded glycolipids. High resolution x-ray structures of apo- and holo-GLTP indicate that major conformational alterations are not responsible for the glycolipid-induced GLTP signature response. Instead, glycolipid binding alters the local environment of Trp-96, which accounts for ∼70% of total emission intensity of three Trp residues in GLTP and provides a stacking platform that aids formation of a hydrogen bond network with the ceramide-linked sugar of the glycolipid headgroup. The changes in Trp signal were used to quantitatively assess human GLTP binding affinity for various lipids including glycolipids containing different sugar headgroups and homogenous acyl chains. The presence of the glycolipid acyl chain and at least one sugar were essential for achieving a low-to-submicromolar dissociation constant that was only slightly altered by increased sugar headgroup complexity. PMID:19270338

Polymer in a pore: Effect of confinement on the free energy barrier

NASA Astrophysics Data System (ADS)

Kumar, Sanjiv; Kumar, Sanjay

2018-06-01

We investigate the transfer of a polymer chain from cis- side to trans- side through two types of pores: cone-shaped channel and flat-channel. Using the exact enumeration technique, we obtain the free energy landscapes of a polymer chain for such systems. We have also calculated the free-energy barrier of a polymer chain attached to the edge of the pore. The model system allows us to calculate the force required to pull polymer from the pore and stall-force to confine polymer within the pore.

Sugar-Sweetened Beverage Demand and Tax Simulation for Federal Food Assistance Participants: A Case of Two New England States.

PubMed

Jithitikulchai, Theepakorn; Andreyeva, Tatiana

2018-06-19

Excessive consumption of sugar-sweetened beverages is a major concern in the efforts to improve diet and reduce obesity in USA, particularly among low-income populations. One of the most commonly proposed strategies to reduce sugar-sweetened beverage consumption is increasing beverage prices through taxation. The objective of this study was to evaluate whether and how price-based policies could reduce sugar-sweetened beverage consumption among participants in the federal Supplemental Nutrition Assistance Program. Using point-of-sale data from a regional supermarket chain (58 stores), we estimated the responsiveness of demand to sugar-sweetened beverage price changes among Supplemental Nutrition Assistance Program-participating families with young children. Own-price and cross-price elasticities for non-alcoholic beverages were estimated using a Quadratic Almost Ideal Demand System model. The study found evidence that a tax-induced sugar-sweetened beverage price increase would reduce total sugar-sweetened beverage purchases among Supplemental Nutrition Assistance Program participants, who were driven by purchase shifts away from taxed sodas and sports drinks to non-taxed beverages (bottled water, juice, milk). The substitution of non-taxed caloric beverages decreases the marginal effects of the sugar-sweetened beverage tax, yet the direct tax effects are large enough to reduce the overall caloric intake, with the average net reduction in monthly calories from sugar-sweetened beverages estimated at around 8% for a half-cent per ounce tax and 16% for a one cent per ounce tax. A beverage price increase in the form of an excise tax would reduce sugar-sweetened beverage consumption and increase healthier beverage purchases among low-income families.

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.

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

PubMed Central

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

2014-01-01

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

Sustainable thermoplastic elastomers derived from cellulose, fatty acid and furfural via ATRP and click chemistry.

PubMed

Yu, Juan; Lu, Chuanwei; Wang, Chunpeng; Wang, Jifu; Fan, Yimin; Chu, Fuxiang

2017-11-15

Cellulose-based thermoplastic elastomers (TPEs) have attracted considerable attention because of their rigid backbone, good mechanical properties, renewable nature and abundance. In the present study, sustainable TPEs based on ethyl cellulose (EC), fatty acid and furfural were generated by the combination of ATRP and "click chemistry". To fabricate sustainable TPEs with higher toughness, a range of polymers, including mono random-copolymer poly(tetrahydrofurfuryl methacrylate-co-lauryl methacrylate) (P(THFMA-co-LMA), dual polymer side chains PTHFMA and PLMA, and mono-block copolymer PTHFMA-b-PLMA, were designed as side chains to fabricate EC brush copolymers with random, dual or block side chain architectures using the "grafting from" and "grafting onto" methods. The multi-armed structures, chemical compositions and phase separation of these EC brush copolymers were confirmed by FT-IR, 1 H NMR, GPC, DSC, TEM and SEM. Overall, three types of EC brush copolymers all exhibited the desired mechanical properties of TPEs. In addition, the EC brush copolymers with dual/block side chain architectures showed higher tensile strength than that of the random polymers with similar compositions. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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

2008-05-01

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

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.

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.

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

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

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.

Genetic Engineering of the Phosphocarrier Protein NPr of the Escherichia coli Phosphotransferase System Selectively Improves Sugar Uptake Activity*

PubMed Central

Lopez-de los Santos, Yossef; Chan, Henry; Cantu, Vito A.; Rettner, Rachael; Sanchez, Filiberto; Zhang, Zhongge; Saier, Milton H.; Soberon, Xavier

2012-01-01

The Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system (PTS) in prokaryotes mediates the uptake and phosphorylation of its numerous substrates through a phosphoryl transfer chain where a phosphoryl transfer protein, HPr, transfers its phosphoryl group to any of several sugar-specific Enzyme IIA proteins in preparation for sugar transport. A phosphoryl transfer protein of the PTS, NPr, homologous to HPr, functions to regulate nitrogen metabolism and shows virtually no enzymatic cross-reactivity with HPr. Here we describe the genetic engineering of a “chimeric” HPr/NPr protein, termed CPr14 because 14 amino acid residues of the interface were replaced. CPr14 shows decreased activity with most PTS permeases relative to HPr, but increases activity with the broad specificity mannose permease. The results lead to the proposal that HPr is not optimal for most PTS permeases but instead represents a compromise with suboptimal activity for most PTS permeases. The evolutionary implications are discussed. PMID:22767600

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).

Cooperative Order-Disorder Transition of Carboxylated Schizophyllan in Water-Dimethylsulfoxide Mixtures.

PubMed

Yoshiba, Kazuto; Dobashi, Toshiaki; Ulset, Ann-Sissel T; Christensen, Bjørn E

2018-06-18

Carboxylated schizophyllan ("sclerox") is a chemically modified polysaccharide obtained by partial periodate oxidation and subsequent chlorite oxidation of schizophyllan, a water-soluble neutral polysaccharide having a β-1,3-linked glucan backbone and a β-1,6-linked d-glucose residue side chain at every third residue of the main chain. The triple helix of schizophyllan in water has a cooperative order-disorder transition associated with the side chains. The transition is strongly affected by the presence (mole fraction) of dimethylsulfoxide (DMSO). In the present study, the solvent effects on the order-disorder transition of sclerox with different degrees of carboxylation (DS) in water-DMSO mixtures were investigated with differential scanning calorimetry and optical rotation. The transition temperature ( T r ) and transition enthalpy (Δ H r ) strongly depended on the mole fraction of DMSO ( x D ). Data were further analyzed with the statistical theory for the linear cooperative transition, taking into account the solvent effect, where DMSO molecules are selectively associated with the unmodified side chains. The modified side chain does not contribute to the transition; hence, Δ H r decreases with increasing DS. The dependence of T r on the DMSO content becomes weaker than that for unmodified schizophyllan. The theoretical analyses indicated that the number of sites binding with the DMSO molecule and the successive ordered sequence of the ordered unit of the triple helix are changed by carboxylation.

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

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

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.

Structural analysis of N-linked carbohydrate chains of funnel web spider (Agelenopsis aperta) venom peptide isomerase.

PubMed

Shikata, Y; Ohe, H; Mano, N; Kuwada, M; Asakawa, N

1998-06-01

The structure of the N-linked carbohydrate chains of peptide isomerase from the venom of the funnel web spider (Agelenopsis aperta) has been analyzed. Carbohydrates were released from peptide isomerase by hydrazinolysis and reductively aminated with 2-aminopyridine. The fluorescent derivatives were purified by phenol/chloroform extraction, followed by size-exclusion HPLC. The structure of the purified pyridylamino (PA-) carbohydrate chains were analyzed by a combination of two-dimensional HPLC mapping, sugar composition analysis, sequential exoglycosidase digestions, and mass spectrometry. The peptide isomerase contains six kinds of N-linked carbohydrate chains of truncated high-mannose type, with a fucose alpha 1-6 linked to the reducing N-acetylglucosamine in approximately 80% of them.

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

PubMed Central

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

1944-01-01

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

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

PubMed

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

1944-10-01

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

Immunochemistry of the Group-Specific Polysaccharide of Nocardia brasiliensis

PubMed Central

Estrada-Parra, Sergio; Zamora, Abel; Bojalil, L. F.

1965-01-01

Estrada-Parra, Sergio (Escuela Nacional de Ciencias Biológicas, México, D.F., México), Abel Zamora, and L. F. Bojalil. Immunochemistry of the group-specific polysaccharide of Nocardia brasiliensis. J. Bacteriol. 90:571–574. 1965.—The group-specific polysaccharide of Nocardia brasiliensis was further purified, yielding an amorphous white material with the following characteristics: [α]D20 = + 48; nitrogen, 0.5%; phosphorus, 0.1%; and ash as sodium, 0.8%. The polymer is made of d-arabinose and d-galactose in a molar ratio of 3:1, and no other sugars were detected. Mild hydrolysis liberates mainly arabinose. The polysaccharide consumes 3.46 μmoles of periodate per mg of polymer in 15 days at 4 C (this value remains constant after 4 more days). Oxidation results in destruction of two of the arabinose, with the formation of two glycerols after borohydride reduction and hydrolysis. The polysaccharide oxidized by periodate and reduced under mild acid hydrolysis at 20 C yields glycerol and a polymer formed by galactose and arabinose (in a ratio of 1:1) which is resistant to a second oxidation. Therefore, the polysaccharide is probably formed by a main chain of glactose linked 1,3 and arabinose linked 1,2 or 1,3 or both, and nonreducing side chains of arabofuranose residues. The intact polysaccharide cross-reacts with sera from patients with active tuberculosis, and this, as well as the homologous reaction, is abolished by oxidation with periodate. PMID:16562050

Lipopolysaccharides of Pantoea agglomerans 7604 and 8674 with structurally related O-polysaccharide chains: Chemical identification and biological properties.

PubMed

Zdorovenko, Evelina L; Kadykova, Alexandra A; Shashkov, Alexander S; Varbanets, Ludmila D; Bulyhina, Tetiana V; Knirel, Yuriy A

2018-02-01

Structurally related O-specific polysaccharide (O-antigen) and lipid A components were obtained by mild acid degradation of the lipopolysaccharides (LPSs) of two strains of bacteria Pantoea agglomerans, 7604 and 8674. Studies by sugar analysis along with 1D and 2D 1 H and 13 C NMR spectroscopy enabled elucidation of the following structures of the O-polysaccharides, which differ only in the linkage configuration of a side-chain glucose residue: R=α-d-Glcp in strain 7604 or β-d-Glcp in strain 8674 Lipid A samples were studied by GC-MS and high-resolution ESI-MS and found to be represented by penta- and tetra-acyl species; lipid A of strain 8674 also included hexaacyl species. A peculiar feature of lipid A of both strains is the presence of the major cis-9-hexadecenoic (palmitoleic) acid, which has not been found in P. agglomerans strains studied earlier. The LPSs of both strains were pyrogenic, reduced the average adhesion and the index of adhesiveness and showed a relatively low level of lethal toxicity. O-antiserum against strain 7604 showed one-way cross-reactivity with the LPS of strain 8674, and O-antisera against both strains cross-reacted with LPSs of some other Р. agglomerans strains but more strains were serologically unrelated. These structural and serological data indicate immunochemical heterogeneity of Р. agglomerans strains and will find demand in classification of Р. agglomerans by O-antigens. Copyright © 2017 Elsevier Ltd. All rights reserved.

ONR Far East Scientific Information Bulletin

DTIC Science & Technology

1990-09-01

In bone, grafting onto a polymer chain, inter- continuous processes, such as reactive extru- chain reactions, formation of interpenetrat- sion and...reaction kinetics, rheology, and side- and end-chain grafting , homopolymer transport phenomena occurring during REX. chain coupling, polymer...the Grafting reactions yield block or graft coupling species becomes a part of the chain, copolymers. Polyethylene, polypropylene, or by

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.

Biosynthetic tailoring of existing ascaroside pheromones alters their biological function in C. elegans

PubMed Central

Zhang, Xinxing; Bhar, Subhradeep; Jones Lipinski, Rachel A; Han, Jungsoo; Feng, Likui

2018-01-01

Caenorhabditis elegans produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we identify a mechanism that enables C. elegans to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation, C. elegans uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for β-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced. PMID:29863473

A comparative study of the sodium content and calories from sugar in toddler foods sold in low- and high-income New York City supermarkets.

PubMed

Samuel, Lalitha; Ethan, Danna; Basch, Corey Hannah; Samuel, Benny

2014-05-07

Information from the nutrition facts labels of toddler foods marketed in low- and high-income New York City zip codes were analyzed for sodium content, the proportion of sugar-derived calories, and presence of sugar and/or high-fructose corn syrup as an added sweetener in the list of ingredients. Among the 272 toddler foods analyzed, more than a quarter were high in sodium, over one-third derived at least 20% their calories from sugar, and more than 41% of the foods had sugar and/or high-fructose corn syrup listed among the first five ingredients. The proportion of foods with such nutritional characteristics did not significantly differ between the low- and high-income neighborhood supermarkets. Median sodium content was highest among "side dishes" and "meals." The proportion of calories derived from sugar was found to be highest among "snacks and yogurt blends" in both low- and high-income neighborhoods and "breakfast foods and cereals" in low-income neighborhoods. When compared to high-income neighborhoods, more than three times the proportion of total calories in "breakfast foods and cereals" sold in low-income neighborhoods were derived from sugar. Since taste preferences established during childhood can have long-lasting influence on dietary habits, it is imperative to limit the promotion of toddler foods that are high in sodium and sugar as well as educate parents to make nutritionally sound decisions at the point of purchase.

Tension Amplification in Molecular Brushes in Solutions and on Substrates

PubMed Central

Panyukov, Sergey; Zhulina, Ekaterina B.; Sheiko, Sergei S.; Randall, Greg C.; Brock, James; Rubinstein, Michael

2009-01-01

Molecular bottle-brushes are highly branched macromolecules with side chains densely grafted to a long polymer backbone. The brush-like architecture allows focusing of the side-chain tension to the backbone and its amplification from the picoNewton to nanoNewton range. The backbone tension depends on the overall molecular conformation and the surrounding environment. Here we study the relation between the tension and conformation of the molecular brushes in solutions, melts, and on substrates. In solutions, we find that the backbone tension in dense brushes with side chains attached to every backbone monomer is on the order of f0N3/8 in athermal solvents, f0N1/3 in θ-solvents, and f0 in poor solvents and melts, where N is the degree of polymerization of side chains, f0≃ kBT/b is the maximum tension in side chains, b is the Kuhn length, kB is Boltzmann constant, and T is absolute temperature. Depending on the side chain length and solvent quality, molecular brushes in solutions develop tension on the order of 10–100 picoNewtons, which is sufficient to break hydrogen bonds. Significant amplification of tension occurs upon adsorption of brushes onto a substrate. On a strongly attractive substrate, maximum tension in the brush backbone is ~ f0N, reaching values on the order of several nanoNewtons which exceed the strength of a typical covalent bond. At low grafting density and high spreading parameter the cross-sectional profile of adsorbed molecular brush is approximately rectangular with thicknes ~bA/S, where A is the Hamaker constant and S is the spreading parameter. At a very high spreading parameter (S > A), the brush thickness saturates at monolayer ~ b. At a low spreading parameter, the cross-sectional profile of adsorbed molecular brush has triangular tent-like shape. In the cross-over between these two opposite cases, covering a wide range of parameter space, the adsorbed molecular brush consists of two layers. Side chains in the lower layer gain surface energy due to the direct interaction with the substrate, while the second layer spreads on the top of the first layer. Scaling theory predicts that this second layer has a triangular cross-section with width R ~ N3/5 and height h ~ N2/5. Using self-consistent field theory we calculate the cap profile y (x) = h (1 − x2/R2)2, where x is the transverse distance from the backbone. The predicted cap shape is in excellent agreement with both computer simulation and experiment. PMID:19673133

An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells

NASA Astrophysics Data System (ADS)

Nilsson, Peter; Magnusson, Karin; Appelqvist, Hanna; Cieslar-Pobuda, Artur; Bäck, Marcus; Kågedal, Bertil; Jonasson, Jon; Los, Marek

2015-10-01

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

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.

20. RW Meyer Sugar Mill: 18761889. Boiling House Interior, 1878. ...

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

20. RW Meyer Sugar Mill: 1876-1889. Boiling House Interior, 1878. View: Remains of south wall. The molasses storage pits are below the floor in the foreground. The remaining piece of floor indicates the form of the entire floor. The sorghum pan and boiling range flue slope from left to right (east to west) and permitted batches of cane juice to flow through the boiling pan by gravity. The beams, joists, truss work are built of northwest pine. The sides and floor boards are built of redwood. The boiling range flue is built of fire-brick, masonry, and portland cement. The corrugated roof appears to be a later addition, not contemporary with mill operation. - R. W. Meyer Sugar Mill, State Route 47, Kualapuu, Maui County, HI

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.

Acid hydrolysis of Jerusalem artichoke for ethanol fermentation

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

Kim, K.; Hamdy, M.K.

1986-01-01

An excellent substrate for ethanol production is the Jerusalem artichoke (JA) tuber (Helianthus tuberosus). This crop contains a high level of inulin that can be hydrolyzed mainly to D-fructose and has several distinct advantages as an energy source compared to others. The potential ethanol yield of ca. 4678 L/ha on good agricultural land is equivalent to that obtained from sugar beets and twice that of corn. When JA is to be used for ethanol fermentation by conventional yeast, it is first converted to fermentable sugars by enzymes or acids although various strains of yeast were used for the direct fermentationmore » of JA extracts. Fleming and GrootWassink compared various acids (hydrochloric, sulfuric, citric, and phosphoric) and strong cation exchange resin for their effectiveness on inulin hydrolysis and reported that no differences were noted among the acids or resin in their influence on inulin hydrolysis. Undesirable side reactions were noted during acid hydrolysis leading to the formation of HMF and 2-(2-hydroxy acetyl) furan. The HMF at a level of 0.1% is known to inhibit growth and ethanol fermentation by yeast. In this study the authors established optimal conditions for complete acid-hydrolysis of JA with minimum side reactions and maximum sugar-ethanol production. A material balance for the ethanol production was also determined.« less

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 thin film surface, buried interfacial, and bulk structures is a first crucial step in understanding the structure-function relationship of such films in order to optimize device performance. An in-depth understanding on how the side-chain influences the interfacial and surface polymer orientation will guide the future molecular structure design of organic semiconductors.

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

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

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

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

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 a phylogenetic classification enabling prediction of specific functions of related enzymes. PMID:24244004

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.

Food and Beverage Selection Patterns among Menu Label Users and Nonusers: Results from a Cross-Sectional Study.

PubMed

Gruner, Jessie; Ohri-Vachaspati, Punam

2017-06-01

By May 5, 2017, restaurants with 20 or more locations nationwide will be required to post calorie information on menus and menu boards. Previous research shows that those who use menu labels purchase fewer calories, but how users are saving calories is unknown. To assess food and beverage selection patterns among menu label users and nonusers. Secondary, cross-sectional analysis using data from a study examining sociodemographic disparities in menu label usage at a national fast-food restaurant chain. Participants were recruited outside restaurant locations, using street-intercept survey methodology. Consenting customers submitted receipts and completed a brief oral survey. Receipt data were used to categorize food and beverage purchases. Side, beverage, and entrée purchases. Sides and beverages were classified as healthier and less-healthy options consistent with the 2015 Dietary Guidelines for Americans. Healthier options contained items promoted in the guidelines, such as whole fruits, vegetables, low-fat dairy, and 100% fruit juice; less-healthy options contained solid fat or added sugar. Entrées were categorized as lower-, medium-, and higher-calorie options, based on quartile cutoffs. Multinomial logistic regression models were used to estimate prevalence ratios (PRs) for purchases among menu label users and nonusers, controlling for sociodemographic characteristics and total price paid. Healthier sides were selected by 7.5% of users vs 2.5% of nonusers; healthier beverages were selected by 34.0% of users vs 11.6% of nonusers; and lowest-calorie entrées were selected by 28.3% of users vs 30.1% of nonusers. Compared with nonusers (n=276), users (n=53) had a higher probability of purchasing healthier sides (PR=5.44; P=0.034), and healthier beverages (PR=3.37; P=0.005). No significant differences were seen in the purchasing patterns of entrées. Targeting educational campaigns to side and beverage purchasing behaviors may increase the effectiveness of menu labeling. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Molecular basis for defect in Alix-binding by alternatively spliced isoform of ALG-2 (ALG-2DeltaGF122) and structural roles of F122 in target recognition.

PubMed

Inuzuka, Tatsutoshi; Suzuki, Hironori; Kawasaki, Masato; Shibata, Hideki; Wakatsuki, Soichi; Maki, Masatoshi

2010-08-06

ALG-2 (a gene product of PDCD6) belongs to the penta-EF-hand (PEF) protein family and Ca2+-dependently interacts with various intracellular proteins including mammalian Alix, an adaptor protein in the ESCRT system. Our previous X-ray crystal structural analyses revealed that binding of Ca2+ to EF3 enables the side chain of R125 to move enough to make a primary hydrophobic pocket (Pocket 1) accessible to a short fragment of Alix. The side chain of F122, facing a secondary hydrophobic pocket (Pocket 2), interacts with the Alix peptide. An alternatively spliced shorter isoform, designated ALG-2DeltaGF122, lacks Gly121Phe122 and does not bind Alix, but the structural basis of the incompetence has remained to be elucidated. We solved the X-ray crystal structure of the PEF domain of ALG-2DeltaGF122 in the Ca2+-bound form and compared it with that of ALG-2. Deletion of the two residues shortened alpha-helix 5 (alpha5) and changed the configuration of the R125 side chain so that it partially blocked Pocket 1. A wall created by the main chain of 121-GFG-123 and facing the two pockets was destroyed. Surprisingly, however, substitution of F122 with Ala or Gly, but not with Trp, increased the Alix-binding capacity in binding assays. The F122 substitutions exhibited different effects on binding of ALG-2 to other known interacting proteins, including TSG101 (Tumor susceptibility gene 101) and annexin A11. The X-ray crystal structure of the F122A mutant revealed that removal of the bulky F122 side chain not only created an additional open space in Pocket 2 but also abolished inter-helix interactions with W95 and V98 (present in alpha4) and that alpha5 inclined away from alpha4 to expand Pocket 2, suggesting acquirement of more appropriate positioning of the interacting residues to accept Alix. We found that the inability of the two-residue shorter ALG-2 isoform to bind Alix is not due to the absence of bulky side chain of F122 but due to deformation of a main-chain wall facing pockets 1 and 2. Moreover, a residue at the position of F122 contributes to target specificity and a smaller side chain is preferable for Alix binding but not favored to bind annexin A11.

Chemical polyglycosylation and nanolitre detection enables single-molecule recapitulation of bacterial sugar export

NASA Astrophysics Data System (ADS)

Kong, Lingbing; Almond, Andrew; Bayley, Hagan; Davis, Benjamin G.

2016-05-01

The outermost protective layer of both Gram-positive and Gram-negative bacteria is composed of bacterial capsular polysaccharides. Insights into the interactions between the capsular polysaccharide and its transporter and the mechanism of sugar export would not only increase our understanding of this key process, but would also help in the design of novel therapeutics to block capsular polysaccharide export. Here, we report a nanolitre detection system that makes use of the bilayer interface between two droplets, and we use this system to study single-molecule recapitulation of sugar export. A synthetic strategy of polyglycosylation based on tetrasaccharide monomers enables ready synthetic access to extended fragments of K30 oligosaccharides and polysaccharides. Examination of the interactions between the Escherichia coli sugar transporter Wza and very small amounts of fragments of the K30 capsular polysaccharide substrate reveal the translocation of smaller but not larger fragments. We also observe capture events that occur only on the intracellular side of Wza, which would complement coordinated feeding by adjunct biosynthetic machinery.

Rhizoctonia resistance conferred by a sugar beet polygalacturonase-inhibiting protein gene

USDA-ARS?s Scientific Manuscript database

Polygalacturonase-inhibiting proteins (PGIPs) are cell wall leucine-rich repeat (LRR) proteins recognized as having a role in plant defense. PGIPs inhibit fungal polygalacturonase (PG) enzymes that break down the polygalacturonate chain in plant cell walls to initiate disease development. The inte...

Analusis by 252Cf plasma desorption mass spectrometry of Bordetella pertussis endotoxin after nitrous deamination

NASA Astrophysics Data System (ADS)

Deprun, C.; Karibian, D.; Caroff, M.

1993-07-01

Endotoxic lipopolysaccharides (LPSs) are the major components of Gram-negative bacterial outer membrane. Like many amphipathic molecules, they pose problems of heterogeneity, purity, solubility, and aggregation. Nevertheless, PDMS has recently have been applied to unmodified endotoxins composed of LPS having uip to five sugar units in their saccharide chain. The B. Pertussis LPSs, most of which have a dodecasaccharide domain, ahve been analysed by classical methods and the masses of the separate lipid and saccharide domains determined after rupture of the bond linking them. However, the acid treatment employed for these and most chemical analyses can also modify structures in the vicinity of the bond. In order to investigate this biologically-important region, the endotoxin was treated to nitrous deamination, which shortens the saccharide chain to five sugars, but preserves the acid-labile region of the LPS. The PDM spectrum of this derivative, which required new conditions for its desorption, confirmed the structure analysis and demonstrated the presence of at least four molecular species.

Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle.

PubMed

Dulal, Pawan; Wright, Daniel; Ashfield, Rebecca; Hill, Adrian V S; Charleston, Bryan; Warimwe, George M

2016-04-29

Development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. Here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. Thermostabilised ChAdOx1-GnGc vaccine stored for 6 months at 25, 37 or 45 ° C elicited comparable Rift Valley Fever virus neutralising antibody titres to those elicited by the 'cold chain' vaccine (stored at -80 ° C throughout) at the same dose, and these were within the range associated with protection against Rift Valley Fever in cattle. The results support the use of sugar-membrane thermostabilised vaccines in target livestock species. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2016-05-01

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

Crystallization and preliminary X-ray analysis of a novel haemagglutinin component of the toxin complex of serotype C Clostridium botulinum.

PubMed

Hayashi, Shintaro; Akiyama, Tomonori; Sagane, Yoshimasa; Miyashita, Shin-Ichiro; Watanabe, Toshihiro; Yajima, Shunsuke; Niwa, Koichi

2014-03-01

The botulinum toxin complex, the causative agent of botulism, passes through the intestinal wall via sugar-chain-dependent cell binding of a haemagglutinin of 33 kDa molecular weight (HA-33). The amino-acid sequence of the C-terminal half of HA-33 of the serotype C strain Yoichi (C-Yoichi) shares only 46% identity with those of the major serotype C strains. Additionally, C-Yoichi HA-33 exhibits a unique sugar-binding specificity. In the present work, C-Yoichi HA-33 was expressed in Escherichia coli and crystallized. Diffraction data were collected at a resolution of 2.2 Å. The crystals belonged to space group R3. The complete detailed protein structure will yield insight into how the unique HA-33 protein recognizes sugar moieties.

Sweet Vector for Gene Delivery: the Sugar Decoration of Polyplexes Reduces Cytotoxicity with a Balanced Effect on Gene Expression.

PubMed

Albuquerque, Lindomar J C; Alavarse, Alex C; Carlan da Silva, Maria C; Zilse, Morgana S; Barth, Maitê T; Bellettini, Ismael C; Giacomelli, Fernando C

2018-02-01

The use of sugar-functionalized polyplexes as a nonviral gene delivery vector with lower cytotoxicity than the well-known polymeric carrier branched polyethyleneimine (BPEI) is investigated. The substitution of primary amine groups in the BPEI chains with lactose residues leads to larger polyplexes, presumably due to the higher amount of polymer required to complete DNA condensation. Nevertheless, the sugar functionalization substantially reduces the cytotoxicity of the assemblies. The nanocomplexes are taken up by the cells to a greater extent, whereas the levels of gene expression are maintained compared to those obtained using BPEI, which is known for its excellent transfection efficiency. Accordingly, the preparation of lower-cytotoxicity polyplexes while maintaining gene expression, which is highly relevant to the field, is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

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

Origin of diverse time scales in the protein hydration layer solvation dynamics: A simulation study

NASA Astrophysics Data System (ADS)

Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

2017-10-01

In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics, we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems, namely, lysozyme, myoglobin, and sweet protein monellin. In these experiments, we mutate the charges of the neighbouring amino acid side chains of certain natural probes (tryptophan) and also freeze the side chain motions. In order to distinguish between different contributions, we decompose the total solvation energy response in terms of various components present in the system. This allows us to capture the interplay among different self- and cross-energy correlation terms. Freezing the protein motions removes the slowest component that results from side chain fluctuations, but a part of slowness remains. This leads to the conclusion that the slow component approximately in the 20-80 ps range arises from slow water molecules present in the hydration layer. While the more than 100 ps component has multiple origins, namely, adjacent charges in amino acid side chains, hydrogen bonded water molecules and a dynamically coupled motion between side chain and water. In addition, the charges enforce a structural ordering of nearby water molecules and helps to form a local long-lived hydrogen bonded network. Further separation of the spatial and temporal responses in solvation dynamics reveals different roles of hydration and bulk water. We find that the hydration layer water molecules are largely responsible for the slow component, whereas the initial ultrafast decay arises predominantly (approximately 80%) due to the bulk. This agrees with earlier theoretical observations. We also attempt to rationalise our results with the help of a molecular hydrodynamic theory that was developed using classical time dependent density functional theory in a semi-quantitative manner.

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.

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/.

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.

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

PubMed Central

Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

High-resolution protein design with backbone freedom.

PubMed

Harbury, P B; Plecs, J J; Tidor, B; Alber, T; Kim, P S

1998-11-20

Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of alpha-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form alpha-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.

Assessing the economic impacts of drought from the perspective of profit loss rate: a case study of the sugar industry in China

NASA Astrophysics Data System (ADS)

Wang, Y.; Lin, L.; Chen, H.

2015-02-01

Natural disasters have enormous impacts on human society, especially on the development of the economy. To support decision making in mitigation and adaption to natural disasters, assessment of economic impacts is fundamental and of great significance. Based on a review of the literature of economic impact evaluation, this paper proposes a new assessment model of economic impact from drought by using the sugar industry in China as a case study, which focuses on the generation and transfer of economic impacts along a simple value chain involving only sugarcane growers and a sugar producing company. A perspective of profit loss rate is applied to scale economic impact with a model based on cost-and-benefit analysis. By using analysis of "with-and-without", profit loss is defined as the difference in profits between disaster-hit and disaster-free scenarios. To calculate profit, analysis on a time series of sugar price is applied. With the support of a linear regression model, an endogenous trend in sugar price is identified, and the time series of sugar price "without" disaster is obtained using an autoregressive error model to separate impact by disasters from the internal trend in sugar price. Unlike the settings in other assessment models, representative sugar prices, which represent value level in disaster-free condition and disaster-hit condition, are integrated from a long time series that covers the whole period of drought. As a result, it is found that in a rigid farming contract, sugarcane growers suffer far more than the sugar company when impacted by severe drought, which may promote the reflections on economic equality among various economic bodies at the occurrence of natural disasters.

Designing interchain and intrachain properties of conjugated polymers for latent optical information encoding

DOE PAGES

Chung, Kyeongwoon; McAllister, Andrew; Bilby, David; ...

2015-09-03

Building molecular-design insights for controlling both the intrachain and the interchain properties of conjugated polymers (CPs) is essential to determine their characteristics and to optimize their performance in applications. However, most CP designs have focused on the conjugated main chain to control the intrachain properties, while the design of side chains is usually used to render CPs soluble, even though the side chains critically affect the interchain packing. Here, we present a straightforward and effective design strategy for modifying the optical and electrochemical properties of diketopyrrolopyrrole-based CPs by controlling both the intrachain and interchain properties in a single system. Themore » synthesized polymers, P1, P2 and P3, show almost identical optical absorption spectra in solution, manifesting essentially the same intrachain properties of the three CPs having restricted effective conjugation along the main chain. However, the absorption spectra of CP films are gradually tuned by controlling the interchain packing through the side-chain design. Here, based on the tailored optical properties, we demonstrate the encoding of latent optical information utilizing the CPs as security inks on a silica substrate, which reveals and conceals hidden information upon the reversible aggregation/deaggregation of CPs.« less

Designing interchain and intrachain properties of conjugated polymers for latent optical information encoding

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

Chung, Kyeongwoon; McAllister, Andrew; Bilby, David

Building molecular-design insights for controlling both the intrachain and the interchain properties of conjugated polymers (CPs) is essential to determine their characteristics and to optimize their performance in applications. However, most CP designs have focused on the conjugated main chain to control the intrachain properties, while the design of side chains is usually used to render CPs soluble, even though the side chains critically affect the interchain packing. Here, we present a straightforward and effective design strategy for modifying the optical and electrochemical properties of diketopyrrolopyrrole-based CPs by controlling both the intrachain and interchain properties in a single system. Themore » synthesized polymers, P1, P2 and P3, show almost identical optical absorption spectra in solution, manifesting essentially the same intrachain properties of the three CPs having restricted effective conjugation along the main chain. However, the absorption spectra of CP films are gradually tuned by controlling the interchain packing through the side-chain design. Here, based on the tailored optical properties, we demonstrate the encoding of latent optical information utilizing the CPs as security inks on a silica substrate, which reveals and conceals hidden information upon the reversible aggregation/deaggregation of CPs.« less

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.

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

PubMed

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

2008-10-03

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

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.

Effect of molecular asymmetry on the charge transport physics of high mobility n-type molecular semiconductors investigated by scanning Kelvin probe microscopy.

PubMed

Hu, Yuanyuan; Berdunov, Nikolai; Di, Chong-an; Nandhakumar, Iris; Zhang, Fengjiao; Gao, Xike; Zhu, Daoben; Sirringhaus, Henning

2014-07-22

We have investigated the influence of the symmetry of the side chain substituents in high-mobility, solution processable n-type molecular semiconductors on the performance of organic field-effect transistors (OFETs). We compare two molecules with the same conjugated core, but either symmetric or asymmetric side chain substituents, and investigate the transport properties and thin film growth mode using scanning Kelvin probe microscopy (SKPM) and atomic force microscopy (AFM). We find that asymmetric side chains can induce a favorable two-dimensional growth mode with a bilayer structure, which enables ultrathin films with a single bilayer to exhibit excellent transport properties, while the symmetric molecules adopt an unfavorable three-dimensional growth mode in which transport in the first monolayer at the interface is severely hindered by high-resistance grain boundaries.

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

Alternative Fluoropolymers to Avoid the Challenges Associated with Perfluorooctanoic Acid

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

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

2008-01-01

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

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

DOEpatents

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

1992-01-01

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

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

DOEpatents

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

1993-01-01

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

Self-generated covalent cross-links in the cell-surface adhesins of Gram-positive bacteria.

PubMed

Baker, Edward N; Squire, Christopher J; Young, Paul G

2015-10-01

The ability of bacteria to adhere to other cells or to surfaces depends on long, thin adhesive structures that are anchored to their cell walls. These structures include extended protein oligomers known as pili and single, multi-domain polypeptides, mostly based on multiple tandem Ig-like domains. Recent structural studies have revealed the widespread presence of covalent cross-links, not previously seen within proteins, which stabilize these domains. The cross-links discovered so far are either isopeptide bonds that link lysine side chains to the side chains of asparagine or aspartic acid residues or ester bonds between threonine and glutamine side chains. These bonds appear to be formed by spontaneous intramolecular reactions as the proteins fold and are strategically placed so as to impart considerable mechanical strength. © 2015 Authors; published by Portland Press Limited.

Engineering E. coli strain for conversion of short chain fatty acids to bioalcohols

PubMed Central

2013-01-01

Background Recent progress in production of various biofuel precursors and molecules, such as fatty acids, alcohols and alka(e)nes, is a significant step forward for replacing the fossil fuels with renewable fuels. A two-step process, where fatty acids from sugars are produced in the first step and then converted to corresponding biofuel molecules in the second step, seems more viable and attractive at this stage. We have engineered an Escherichia coli strain to take care of the second step for converting short chain fatty acids into corresponding alcohols by using butyrate kinase (Buk), phosphotransbutyrylase (Ptb) and aldehyde/alcohol dehydrogenase (AdhE2) from Clostridium acetobutylicum. Results The engineered E. coli was able to convert butyric acid and other short chain fatty acids of chain length C3 to C7 into corresponding alcohols and the efficiency of conversion varied with different E. coli strain type. Glycerol proved to be a better donor of ATP and electron as compared to glucose for converting butyric acid to butanol. The engineered E. coli was able to tolerate up to 100 mM butyric acid and produced butanol with the conversion rate close to 100% under anaerobic condition. Deletion of native genes, such as fumarate reductase (frdA) and alcohol dehydrogenase (adhE), responsible for side products succinate and ethanol, which act as electron sink and could compete with butyric acid uptake, did not improve the butanol production efficiency. Indigenous acyl-CoA synthetase (fadD) was found to play no role in the conversion of butyric acid to butanol. Engineered E. coli was cultivated in a bioreactor under controlled condition where 60 mM butanol was produced within 24 h of cultivation. A continuous bioreactor with the provision of cell recycling allowed the continuous production of butanol at the average productivity of 7.6 mmol/l/h until 240 h. Conclusions E. coli engineered with the pathway from C. acetobutylicum could efficiently convert butyric acid to butanol. Other short chain fatty acids with the chain length of C3 to C7 were also converted to the corresponding alcohols. The ability of engineered strain to convert butyric acid to butanol continuously demonstrates commercial significance of the system. PMID:24020887

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

PubMed

Shah, Dhawal; Shaikh, Abdul Rajjak

2016-01-01

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

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

Optimization and Implementation of Long Nerve Allografts

DTIC Science & Technology

2013-03-01

chondroitin   sulfate  proteoglycans.    All  processing  methods   include  the  same  treatment  step  with...methods  effectively  eliminate  the   chondroitin   sulfate  side-­‐chains  after  detergent   extractions...the  three   processing  methods  effectively  eliminate  the   chondroitin   sulfate  side-­‐chains  and  yet

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.

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

PubMed Central

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

2012-01-01

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

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.

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

PubMed

Singh, J; Thornton, J M

1990-02-05

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

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

PubMed

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

2017-01-01

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

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.

Roles of urea and TMAO on the interaction between extended non-polar peptides

NASA Astrophysics Data System (ADS)

Su, Zhaoqian; Dias, Cristiano

Urea and trimethylamine n-oxide (TMAO) are small molecules known to destabilize and stabilize, respectively, the structure of proteins when added to aqueous solution. To unravel the molecular mechanisms of these cosolvents on protein structure we perform explicit all-atom molecular dynamics simulations of extended poly-alanine and polyleucine dimers. We use an umbrella sampling protocol to compute the potential of mean force (PMF) of dimers at different concentrations of urea and TMAO. We find that the large non-polar side chain of leucine is affected by urea whereas backbone atoms and alanine's side chain are not. Urea is found to occupy positions between leucine's side chains that are not accessible to water. This accounts for extra Lennard-Jones bonds between urea and side chains that favors the unfolded state. These bonds compete with urea-solvent interactions that favor the folded state. The sum of these two energetic terms provide the enthalpic driving force for unfolding. We show here that this enthalpy correlate with the potential of mean force of poly-leucine dimers. Moreover, the framework developed here is general and may be used to provide insights into effects of other small molecules on protein interactions. The effect of the TMAO will be in the presentation. Department of Physics, University Heights, Newark, New Jersey, 07102-1982.

Quantitative Protein Topography Analysis and High-Resolution Structure Prediction Using Hydroxyl Radical Labeling and Tandem-Ion Mass Spectrometry (MS)*

PubMed Central

Kaur, Parminder; Kiselar, Janna; Yang, Sichun; Chance, Mark R.

2015-01-01

Hydroxyl radical footprinting based MS for protein structure assessment has the goal of understanding ligand induced conformational changes and macromolecular interactions, for example, protein tertiary and quaternary structure, but the structural resolution provided by typical peptide-level quantification is limiting. In this work, we present experimental strategies using tandem-MS fragmentation to increase the spatial resolution of the technique to the single residue level to provide a high precision tool for molecular biophysics research. Overall, in this study we demonstrated an eightfold increase in structural resolution compared with peptide level assessments. In addition, to provide a quantitative analysis of residue based solvent accessibility and protein topography as a basis for high-resolution structure prediction; we illustrate strategies of data transformation using the relative reactivity of side chains as a normalization strategy and predict side-chain surface area from the footprinting data. We tested the methods by examination of Ca+2-calmodulin showing highly significant correlations between surface area and side-chain contact predictions for individual side chains and the crystal structure. Tandem ion based hydroxyl radical footprinting-MS provides quantitative high-resolution protein topology information in solution that can fill existing gaps in structure determination for large proteins and macromolecular complexes. PMID:25687570

Ion Trap Collisional Activation of c and z• Ions Formed via Gas-Phase Ion/Ion Electron Transfer Dissociation

PubMed Central

Han, Hongling; Xia, Yu; McLuckey, Scott A.

2008-01-01

A series of c- and z•-type product ions formed via gas-phase electron transfer ion/ion reactions between protonated polypeptides with azobenzene radical anions are subjected to ion trap collision activation in a linear ion trap. Fragment ions including a-, b-, y-type and ammonia-loss ions are typically observed in collision induced dissociation (CID) of c ions, showing almost identical CID patterns as those of the C-terminal amidated peptides consisting of the same sequences. Collisional activation of z• species mainly gives rise to side-chain losses and peptide backbone cleavages resulting in a-, b-, c-, x-, y-and z-type ions. Most of the fragmentation pathways of z• species upon ion trap CID can be accounted for by radical driven processes. The side-chain losses from z• species are different from the small losses observed from the charge-reduced peptide molecular species in electron transfer dissociation (ETD), which indicates rearrangement of the radical species. Characteristic side-chain losses are observed for several amino acid residues, which are useful to predict their presence in peptide/protein ions. Furthermore, the unique side-chain losses from leucine and isoleucine residues allow facile distinction of these two isomeric residues. PMID:17608403

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

NASA Astrophysics Data System (ADS)

Macleod, Neil A.; Simons, John P.

2002-10-01

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

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.

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

Thermoresponsive light scattering device utilizing surface behavior effects between polyimide and an ionic liquid-water mixture exhibiting lower critical solution temperature (LCST)-type phase separation

NASA Astrophysics Data System (ADS)

Goda, Kazuya; Takatoh, Kohki; Funasako, Yusuke; Inokuchi, Makoto

2018-06-01

We proposed a thermoresponsive light scattering device that utilizes the surface behavior between polyimide and an ionic liquid-water mixture exhibiting lower critical solution temperature (LCST)-type phase separation. The LCST behavior for an ionic liquid device utilizing the polyimide with and without alkyl side chains was investigated. In the here-reported ionic liquid device that utilized the polyimide with alkyl side chains, [nBu4P][CF3COO] droplets were generated by phase separation—they were predominantly formed at the alkyl surface by a surface pinning effect. A stable transmittance in the opaque state could be obtained with this device. In contrast, an ionic liquid device using polyimide without alkyl side chains deteriorated transmittance in the opaque state because there was no surface pinning effect. Additionally, the viewing angle, contrast ratio, and heat cycle testing of this ionic liquid device with polyimide with alkyl side chains were also investigated. The results indicated that no parallax was obtained and that the ionic liquid device has a stable transmittance (verified by heat cycle testing). This unique device is expected to find use in the smart window applications that are activated by temperature changes.

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.

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

[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.

Extraction and determination of chondroitin sulfate from fish processing byproducts

USDA-ARS?s Scientific Manuscript database

Chondroitin sulfate (CS) refers to a group of sulfated glycosaminoglycan containing a chain of alternating N-acetylgalactosamine and glucuronic acid sugars. It is a major component of the extracellular matrix of cartilage and attached to proteins. CS is usually an over the counter dietary supplement...

Exploring glycogen biosynthesis through Monte Carlo simulation.

PubMed

Zhang, Peng; Nada, Sharif S; Tan, Xinle; Deng, Bin; Sullivan, Mitchell A; Gilbert, Robert G

2018-05-08

Glycogen, a complex branched polymer of glucose (average chain length ~10 monomer units), is the blood-sugar reservoir in humans and other animals. Certain aspects of its molecular structure relevant to its biological functions are currently unamenable to experimental exploration. Knowledge of these is needed to develop future models for quantitative data-fitting to obtain mechanistic understanding of the biosynthetic processes that give rise to glycogen structure. Monte Carlo simulations of the biosynthesis of this structure with realistic macromolecular parameters reveal how chain growth and stoppage (the latter assumed to be through both the action of glycogen branching enzyme and other degradative enzymes, and by hindrance) control structural features. The simulated chain-length, pair-distance and radial density distributions agree semi-quantitatively with the limited available data. The simulations indicate that a steady state in molecular structure and size is rapidly obtained, that molecular density reaches a maximum near the center of the particle (not at the periphery, as is the case with dendrimers), and that particle size is controlled by both enzyme activity and hindrance. This knowledge will aid in the understanding of diabetes (loss of blood-sugar control), which has been found to involve subtle differences in glycogen molecular structure. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

Wang, Shu; Robertson, Megan L

2015-06-10

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