title: Mannopeptimycins, novel antibacterial glycopeptides from Streptomyces hygroscopicus, LL-AC98.
abstract: A series of novel antibiotics with activity against methicillin-resistant staphylococci and vancomycin-resistant enterococci has been purified, and their structures have been characterized using spectroscopic analyses and chemical conversions. These antibiotics, designated mannopeptimycins alpha-epsilon (1-5), are glycosylated cyclic hexapeptides containing two stereoisomers of an unprecedented amino acid, alpha-amino-beta-[4'-(2'-iminoimidazolidinyl)]-beta-hydroxypropionic acid (Aiha), as a distinguishing feature. The cyclic peptide core of these antibiotics is attached to a mannosyl monosaccharide moiety in 2 and to mannosyl monosaccharide and disaccharide moieties in 1, 3, 4, and 5. The presence and position of an isovaleryl group in the terminal mannose (Man-B) in 3-5 are critical for retaining antibacterial potency.
authors.affiliation: Department of Natural Products Chemistry, Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. heh@wyeth.com
authors.forename: Haiyin
authors.initials: H
authors.lastname: He
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Williamson
authors.forename: Bo
authors.initials: B
authors.lastname: Shen
authors.forename: Edmund I
authors.initials: EI
authors.lastname: Graziani
authors.forename: Hui Y
authors.initials: HY
authors.lastname: Yang
authors.forename: Subas M
authors.initials: SM
authors.lastname: Sakya
authors.forename: Pete J
authors.initials: PJ
authors.lastname: Petersen
authors.forename: Guy T
authors.initials: GT
authors.lastname: Carter
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D006020:Glycopeptides; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides