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. HPLC, NMR, and molecular dynamic studies of GMDP reveal a slow equilibrium of folded α and extended β anomeric forms. The β‐form is responsible for the immunoadjuvant activity of gluosaminyl‐muramyl‐dipeptide sample, the α‐anomer being practically inactive.