Semisynthetic approaches to laspartomycin analogues.
Laspartomycin C (1), a lipopeptide antibiotic related to amphomycin, consists of a cyclic peptide core and an aspartic acid unit external to the core and linking this to a C15-2,3-unsaturated fatty acid. This was reported initially to be active against Staphylococcus aureus, and more recent studies have shown that it is active against VRE, VISA, and MRSA isolates. The enzymatic cleavage of the fatty acid tail was accomplished with a deacylase produced by Actinoplanes utahensis and resulted in two peptides, designated Peptide 1 and Peptide 2. Semisynthetic derivatives of both peptides have been made, and the principal requirement for biological activity appears to be the presence of an acylaspartic acid.
Curran
William V
WV
BioSource Pharm, Inc., Spring Valley, NY 10977, USA. Biosource@prodigy.net
Leese
Richard A
RA
Jarolmen
Howard
H
Borders
Donald B
DB
Dugourd
Dominique
D
Chen
Yuchen
Y
Cameron
Dale R
DR
D000581:Amidohydrolases / Q000378:metabolism*; D000619:Aminohydrolases / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D055666:Lipopeptides; D016106:Methicillin Resistance / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008848:Micromonosporaceae / Q000201:enzymology; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D014364:Tryptophan / Q000737:chemistry; D020713:Vancomycin Resistance / Q000187:drug effects
D000900:Anti-Bacterial Agents; D055666:Lipopeptides; D009842:Oligopeptides; D010456:Peptides, Cyclic; C519250:laspartomycin C; C004423:amphomycin; D014364:Tryptophan; D000581:Amidohydrolases; C519252:deacylase, Actinoplanes utahensis; D000619:Aminohydrolases