MM 45289, a potent glycopeptide antibiotic which interacts weakly with diacetyl-L-lysyl-D-alanyl-D-alanine.
MM 45289 (A82846A, eremomycin), a glycopeptide antibiotic of the vancomycin type, was confirmed to have improved antibacterial activity over vancomycin. However its affinity (Ka) for the target site peptide mimetic diacetyl-L-lysyl-D-alanyl-D-alanine (DALAA) was 23-fold lower. Concentrations of DALAA required to reverse the antibacterial activity of MM 45289 were in the order of 10 to 50-fold higher than for vancomycin. These results have implications for both mode of action studies and mechanism-based screening strategies for this class of antibiotic.
Good
V M
VM
Beecham Pharmaceuticals Research Division, Betchworth, Surrey, UK.
Gwynn
M N
MN
Knowles
D J
DJ
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology*; D006020:Glycopeptides / Q000378:metabolism / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013210:Staphylococcus / Q000187:drug effects*; D014640:Vancomycin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004151:Dipeptides; D006020:Glycopeptides; D007773:Lactates; D008024:Ligands; D009842:Oligopeptides; C043631:diacetyllysylalanine lactate; C053759:eremomycin; D014640:Vancomycin