GMDP: unusual physico‐chemical and biological properties of the anomeriс forms

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.