title: Design and synthesis of 16-membered cyclopeptides active against vancomycin-resistant Enterococci (VRE).
abstract: The design, synthesis and antibiotic activities of the modified carboxylate binding pocket (D-O-E ring) of vancomycin (1) are summarized in this short account. The preliminary structure-activity relationship (SAR) studies indicated that both the structure of the 16-membered macrocycle including the absolute configuration of the modified AA4 unit and the presence of a hydrophobic chain were important for anti-VRE activities of these series of synthetic analogues. Compounds 9c and 9d in which the central amino acid (AA4) of vancomycin was replaced by (2R,3R)-α-hydroxy-β-amino acid and (2R,3R)-α,β-diamino acid, respectively, were found to be useful templates in searching for active compounds against both vancomycin-sensitive and -resistant strains. Two of these compounds (16d and 16n) having an elongated peptide chain at the C-terminal were found to be active against a broad spectrum of both vancomycin-sensitive (Staphylococcus aureus) and -resistant strains (E. faecium, E. faecalis).
authors.affiliation: Laboratory of Synthesis and Natural Products, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne, EPFL-SB-ISIC-LSPN, CH-1015 Lausanne, Switzerland.
authors.forename: Jieping
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D014640:Vancomycin