GMDP: unusual physico-chemical and biological properties of the anomeri? forms

Disaccharide containing unit of peptidoglycan from bacterial cell wall, N-acetyl-d-glucosaminyl-N-acetylmuramyl-l-alanyl-d-glutaminamide (glu?osaminyl-muramyl-dipeptide) registered in Russia as an immunomodulatory drug, is shown to participate in slow equilibrium of and anomeric forms. Data of NMR spectra and molecular dynamics indicate that the -anomer predominantly acquires a folded conformation stabilized by intramolecular hydrogen bond between the alanyl carbonyl and muramyl NH proton. The -form displays a considerable fraction of extended, non-hydrogen bonded structures. In the standard immunoadjuvant test system, the -form is practically inactive, and the activity of the equilibrium mixture with :=68:32 ratio is due to the presence of -anomer. Such unique - selectivity of biological action must be considered at the design of related immunoactive glycopeptides. Copyright (c) 2015 European Peptide Society and John Wiley & Sons, Ltd.