title: GMDP: unusual physico-chemical and biological properties of the anomeriс forms.
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.
authors.affiliation: M.M.Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Meshcheryakova
authors.affiliation: M.M.Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Konstantin S
authors.initials: KS
authors.lastname: Mineev
authors.affiliation: M.M.Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Pavel E
authors.initials: PE
authors.lastname: Volynski
authors.affiliation: M.M.Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Andronova
authors.affiliation: M.M.Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vadim T
authors.initials: VT
authors.lastname: Ivanov
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006020:Glycopeptides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010457:Peptidoglycan / Q000737:chemistry*
chemical_list: D006020:Glycopeptides; D010457:Peptidoglycan; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: NMR; activity; adjuvant; anomers; computer simulation; equilibrium; glycopeptide