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GMDP: unusual physico‐chemical and biological properties of the anomeriс forms
Author(s) -
Meshcheryakova Elena A.,
Mineev Konstantin S.,
Volynski Pavel E.,
Andronova Tatiana M.,
Ivanov Vadim T.
Publication year - 2015
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2796
Subject(s) - anomer , chemistry , immunoadjuvant , hydrogen bond , muramyl dipeptide , peptidoglycan , intramolecular force , stereochemistry , disaccharide , proton nmr , dipeptide , combinatorial chemistry , peptide , biochemistry , molecule , organic chemistry , cell wall , in vitro , adjuvant , medicine
Disaccharide containing unit of peptidoglycan from bacterial cell wall, N ‐acetyl‐ d ‐glucosaminyl‐ N ‐acetylmuramyl‐ l ‐alanyl‐ d ‐glutaminamide (gluсosaminyl‐muramyl‐dipeptide) registered in Russia as an immunomodulatory drug, is shown to participate in slow equilibrium of α and β anomeric forms. Data of NMR spectra and molecular dynamics indicate that the α ‐anomer predominantly acquires a folded conformation stabilized by intramolecular hydrogen bond between the alanyl carbonyl and muramyl NH proton. The β ‐form displays a considerable fraction of extended, non‐hydrogen bonded structures. In the standard immunoadjuvant test system, the α ‐form is practically inactive, and the activity of the equilibrium mixture with α : β = 68 : 32 ratio is due to the presence of β ‐anomer. Such unique α–β selectivity of biological action must be considered at the design of related immunoactive glycopeptides. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.