Journal of Peptide Science 2015-09-01

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

Elena A Meshcheryakova, Konstantin S Mineev, Pavel E Volynski, Tatiana M Andronova, Vadim T Ivanov

Index: J. Pept. Sci. 21 , 717-22, (2015)

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Abstract

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.