The conformational restriction of synthetic peptides, including a malaria peptide, for use as immunogens

1989 ◽  
Vol 323 (1217) ◽  
pp. 565-572 ◽  
Keyword(s):  
Hydrogen Bond ◽  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Synthetic Peptides ◽  
Synthetic Methods ◽  
Amide Hydrogen ◽  
Conformational Restriction ◽  
Conformationally Restricted ◽  
New Strategy

A new strategy is advanced for the conformational restriction of peptidyl immunogens. Our approach is to replace putative amide-amide hydrogen bonds with covalent hydrogen-bond mimics. Because on average every other amino acid in a protein engages in this bond, the syntheses of diversely shaped peptides can be contemplated. Synthetic methods for introducing a potential hydrogen-bond mimic into a peptide with α-helical potential is reported and the structural consequences are discussed. The replacement of the hydrogen bond with a chemical link will modify as well as shape the peptide. To explore the consequences of these changes, a potential synthetic vaccine for malaria, the repeating tetrapeptide Asn-Pro-Asn-Ala, was conformationally restricted. Antibodies to the shaped malarial peptide showed a strong cross reaction with Plasmodium falciparum sporozoites.

scholarly journals Crystal structure of the tripeptideN-(benzyloxycarbonyl)glycylglycyl-L-norvaline

2015 ◽  
Vol 71 (3) ◽  
pp. o216-o217
Author(s):  
Sumesh Nicholas
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Crystal Lattice ◽  
Side Chain ◽  
Screw Axis ◽  
Terminal Amino Acid ◽  
Backbone Conformation ◽  
Terminal Amino

The title tripeptide, C17H23N3O6, contains a nonproteinogenic C-terminal amino acid residue, norvaline, which is an isomer of the amino acid valine. Norvaline, unlike valine, has an unbranched side chain. The molecule has a Gly–Gly segment which adopts an extended conformation. The norvaline residue also adopts an extended backbone conformation while its side chain has ag+tconformation. In the crystal lattice, N—H...O and O—H...O hydrogen bonds stabilize the packing. Molecules translated along the crystallographicaaxis associate through an N—H...O hydrogen bond. The remaining three hydrogen bonds are between molecules related by a21screw axis.

scholarly journals Effective prediction of short hydrogen bonds in proteins via machine learning method

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengmin Zhou ◽  
Yuanhao Liu ◽  
Sijian Wang ◽  
Lu Wang
Keyword(s):  
Machine Learning ◽  
Hydrogen Bond ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Protein Structures ◽  
Decomposition Analysis ◽  
Energy Decomposition Analysis ◽  
Donor And Acceptor ◽  
Wide Range ◽  
Short Hydrogen Bonds

AbstractShort hydrogen bonds (SHBs), whose donor and acceptor heteroatoms lie within 2.7 Å, exhibit prominent quantum mechanical characters and are connected to a wide range of essential biomolecular processes. However, exact determination of the geometry and functional roles of SHBs requires a protein to be at atomic resolution. In this work, we analyze 1260 high-resolution peptide and protein structures from the Protein Data Bank and develop a boosting based machine learning model to predict the formation of SHBs between amino acids. This model, which we name as machine learning assisted prediction of short hydrogen bonds (MAPSHB), takes into account 21 structural, chemical and sequence features and their interaction effects and effectively categorizes each hydrogen bond in a protein to a short or normal hydrogen bond. The MAPSHB model reveals that the type of the donor amino acid plays a major role in determining the class of a hydrogen bond and that the side chain Tyr-Asp pair demonstrates a significant probability of forming a SHB. Combining electronic structure calculations and energy decomposition analysis, we elucidate how the interplay of competing intermolecular interactions stabilizes the Tyr-Asp SHBs more than other commonly observed combinations of amino acid side chains. The MAPSHB model, which is freely available on our web server, allows one to accurately and efficiently predict the presence of SHBs given a protein structure with moderate or low resolution and will facilitate the experimental and computational refinement of protein structures.

Four oxoindole-linked α-alkoxy-β-amino acid derivatives

2015 ◽  
Vol 71 (4) ◽  
pp. 322-329 ◽  
Author(s):  
Krishnan Ravikumar ◽  
Balasubramanian Sridhar ◽  
Jagadeesh Babu Nanubolu ◽  
Tamilselvan Rajasekaran ◽  
Basi Venkata Subba Reddy
Keyword(s):  
Hydrogen Bond ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Benzyl Alcohol ◽  
Chemical Reaction ◽  
Amide Group ◽  
Amino Acid Derivatives ◽  
Relative Configuration ◽  
Extended Conformation ◽  
Hydrogen Bond Interactions

Four structures of oxoindolyl α-hydroxy-β-amino acid derivatives, namely, methyl 2-{3-[(tert-butoxycarbonyl)amino]-1-methyl-2-oxoindolin-3-yl}-2-methoxy-2-phenylacetate, C24H28N2O6, (I), methyl 2-{3-[(tert-butoxycarbonyl)amino]-1-methyl-2-oxoindolin-3-yl}-2-ethoxy-2-phenylacetate, C25H30N2O6, (II), methyl 2-{3-[(tert-butoxycarbonyl)amino]-1-methyl-2-oxoindolin-3-yl}-2-[(4-methoxybenzyl)oxy]-2-phenylacetate, C31H34N2O7, (III), and methyl 2-[(anthracen-9-yl)methoxy]-2-{3-[(tert-butoxycarbonyl)amino]-1-methyl-2-oxoindolin-3-yl}-2-phenylacetate, C38H36N2O6, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α-diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts ananticonformation, whereas the conformation issynin esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether-linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen-bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen-bond interactions.

Carbon-Hydrogen Bond Functionalization in Aqueous Medium: A Brief Review

2019 ◽  
Vol 6 (3) ◽  
pp. 184-197 ◽  
Author(s):  
Rajib Sarkar ◽  
Chhanda Mukhopadhyay
Keyword(s):  
Hydrogen Bond ◽  
Hydrogen Bonds ◽  
Aqueous Medium ◽  
Synthetic Methods ◽  
Environmentally Benign ◽  
Current Development ◽  
Significant Development ◽  
Bond Functionalization ◽  
Considerable Research ◽  
Green Conditions

In the last few decades, considerable research has led to the introduction of selective and efficient green as well as sustainable synthetic methods of functionalization of carbon-hydrogen bonds to form new carbon-carbon and carbon-heteroatom bonds. In this emerging field, significant development has been attained under various environmentally benign conditions including aqueous medium. In this review, we have summarized the current development of C-H functionalization carried out in an aqueous medium and its synthetic applications according to carbon-carbon and carbon-heteroatom bond formations under green conditions.

scholarly journals Main Chain Hydrogen Bond Interactions in the Binding of Proline-rich Gluten Peptides to the Celiac Disease-associated HLA-DQ2 Molecule

2005 ◽  
Vol 280 (23) ◽  
pp. 21791-21796 ◽  
Author(s):  
Elin Bergseng ◽  
Jiang Xia ◽  
Chu-Young Kim ◽  
Chaitan Khosla ◽  
Ludvig M. Sollid
Keyword(s):  
Hydrogen Bond ◽  
Major Histocompatibility Complex ◽  
Celiac Disease ◽  
Hydrogen Bonds ◽  
Main Chain ◽  
Amide Hydrogen ◽  
Hydrogen Bond Interactions ◽  
Histocompatibility Complex ◽  
Gluten Peptides ◽  
Hla Dq2

Binding of peptide epitopes to major histocompatibility complex proteins involves multiple hydrogen bond interactions between the peptide main chain and major histocompatibility complex residues. The crystal structure of HLA-DQ2 complexed with the αI-gliadin epitope (LQPFPQPELPY) revealed four hydrogen bonds between DQ2 and peptide main chain amides. This is remarkable, given that four of the nine core residues in this peptide are proline residues that cannot engage in amide hydrogen bonding. Preserving main chain hydrogen bond interactions despite the presence of multiple proline residues in gluten peptides is a key element for the HLA-DQ2 association of celiac disease. We have investigated the relative contribution of each main chain hydrogen bond interaction by preparing a series of N-methylated αI epitope analogues and measuring their binding affinity and off-rate constants to DQ2. Additionally, we measured the binding of αI-gliadin peptide analogues in which norvaline, which contains a backbone amide hydrogen bond donor, was substituted for each proline. Our results demonstrate that hydrogen bonds at P4 and P2 positions are most important for binding, whereas the hydrogen bonds at P9 and P6 make smaller contributions to the overall binding affinity. There is no evidence for a hydrogen bond between DQ2 and the P1 amide nitrogen in peptides without proline at this position. This is a unique feature of DQ2 and is likely a key parameter for preferential binding of proline-rich gluten peptides and development of celiac disease.

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