Mannopeptimycins, novel antibacterial glycopeptides from Streptomyces hygroscopicus, LL-AC98.
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.
He
Haiyin
H
Department of Natural Products Chemistry, Chemical Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA. heh@wyeth.com
Williamson
R Thomas
RT
Shen
Bo
B
Graziani
Edmund I
EI
Yang
Hui Y
HY
Sakya
Subas M
SM
Petersen
Pete J
PJ
Carter
Guy T
GT
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*
D000900:Anti-Bacterial Agents; D006020:Glycopeptides