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

Авторы: Elena A. Meshcheryakova, Konstantin S. Mineev, Pavel E. Volynski, Tatiana M. Andronova, Vadim T. Ivanov
Издание: Journal of Peptide Sciens. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/psc.2796
Год: 2015

Аннотация: Disaccharide containing unit of peptidoglycan from bacterial cell wall, N-acetyl-D-glucosaminyl-N-acetylmuramyl-L-alanyl-Dglutaminamide (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.

Ключевые слова: glycopeptide, anomers, equilibrium, NMR, computer simulation, adjuvant, activity,