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.