Iterative Chemical Engineering of Vancomycin Leads to Novel Vancomycin Analogs With a High in Vitro Therapeutic Index.

ABSTRACT: Vancomycin is a glycopeptide antibiotic that inhibits transpeptidation during cell wall synthesis by binding to the D-Ala-D-Ala termini of lipid II. For long, it has been used as a last resort antibiotic. However, since the emergence of the first vancomycin-resistant enterococci in 1987, vancomycin resistance has become widespread, especially in hospitals. We have synthesized and evaluated 110 vancomycin analogs modified at the C-terminal carboxyl group of the heptapeptide moiety with R₂NHR₁NH₂ substituents. Through iterative optimizations of the substituents, we identified vancomycin analogs that fully restore (or even exceed) the original inhibitory activity against vancomycin-resistant enterococci (VRE), vancomycin-intermediate (VISA) and vancomycin-resi

SUBMITTER: Mishra NM 

PROVIDER: S-EPMC6001238 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature