Open AccessDesign and Synthesis of 16-Membered Cyclopeptides Active Against Vancomycin-resistant Enterococci (VRE)
Author(s) -
Jieping Zhu
Publication year - 2013
Publication title -
chimia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.387
H-Index - 55
eISSN - 2673-2424
pISSN - 0009-4293
DOI - 10.2533/chimia.2013.916
Subject(s) - vancomycin , stereochemistry , chemistry , vancomycin resistant enterococci , amino acid , peptide , enterococcus faecium , combinatorial chemistry , amino acid residue , antibiotics , staphylococcus aureus , bacteria , biology , biochemistry , peptide sequence , genetics , gene
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)-?-hydroxy-?-amino acid and (2R,3R)-?,?-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).