Synthesis and preliminary biological characterization of new semisynthetic derivatives of ramoplanin.

Ramoplanin is a glycolipodepsipeptide antibiotic active against Gram-positive bacteria including vancomycin-resistant enterococci. Ramoplanin inhibits bacterial cell wall biosynthesis by a mechanism different from that of glycopeptides and hence does not show cross-resistance with these antibiotics. The systemic use of ramoplanin has been so far prevented because of its low local tolerability when injected intravenously.

Differential inhibition of Staphylococcus aureus PBP2 by glycopeptide antibiotics.

The glycopeptide antibiotics prevent maturation of the bacterial cell wall by binding to the terminal d-alanyl-d-alanine moiety of peptidoglycan precursors, thereby inhibiting the enzymes involved in the final stages of peptidoglycan synthesis. However, there are significant differences in the biological activity of particular glycopeptide derivatives that are not related to their affinity for d-Ala-d-Ala. We compare the ability of vancomycin and a set of clinically relevant glycopeptides to inhibit Staphylococcus aureus PBP2 (penicillin binding protein), the major transglycosylase in a clinically relevant pathogen, S.