Chlorobiphenyl-desleucyl-vancomycin inhibits the transglycosylation process required for peptidoglycan synthesis in bacteria in the absence of dipeptide binding

• DOI: 10.1111/j.1574-6968.2000.tb08959.x
• Publication Date: 2006-01-10T07:51:59Z
• Authors: Robert C Goldman; Eugene R Baizman; Clifford B Longley; Arthur A Branstrom
• Keywords: Lipid II; Pentapeptide repeat; Muramyl dipeptide

Novel glycopeptide analogs are known that have activity on vancomycin resistant enterococci despite the fact primary site for drug interaction, D-ala-D-ala, is replaced with D-ala-D-lactate. The mechanism of action these compounds may involve dimerization and/or membrane binding, thus enhancing interaction D-ala-D-lactate, or a direct transglycosylase enzymes involved in peptidoglycan polymerization. We evaluated ability (V), desleucyl-vancomycin (desleucyl-V), chlorobiphenyl-vancomycin (CBP-V), and chlorobiphenyl-desleucyl-vancomycin (CBP-desleucyl-V) to inhibit (a) synthesis vitro using UDP-muramyl-pentapeptide UDP-muramyl-tetrapeptide substrates (b) growth enterococci. Compared V CBP-V, CBP-desleucyl-V retained equivalent potency assays, whereas desleucyl-V was inactive. In addition, caused accumulation N-acetylglucosamine-beta-1, 4-MurNAc-pentapeptide-pyrophosphoryl-undecaprenol (lipid II). These data show inhibits at transglycosylation stage absence binding dipeptide.