Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.

Published

Journal Article

The peptide antibiotic ramoplanin is highly effective against several drug-resistant gram-positive bacteria, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), two important opportunistic human pathogens. Ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by binding to Lipid intermediates I and II at a location different than the N-acyl-D-Ala-D-Ala dipeptide site targeted by vancomycin. Lipid I/II capture physically occludes these substrates from proper utilization by the late-stage PG biosynthesis enzymes MurG and the transglycosylases. Key structural features of ramoplanin responsible for antibiotic activity and PG molecular recognition have been discovered by antibiotic semisynthetic modification in conjunction with NMR analyses. These results help define a minimalist ramoplanin pharmacophore and introduce the possibility of generating ramoplanin-derived peptide or peptidomimetic antibiotics for use against VRE, MRSA, and related pathogens.

Full Text

Duke Authors

Cited Authors

  • Cudic, P; Behenna, DC; Kranz, JK; Kruger, RG; Wand, AJ; Veklich, YI; Weisel, JW; McCafferty, DG

Published Date

  • August 2002

Published In

Volume / Issue

  • 9 / 8

Start / End Page

  • 897 - 906

PubMed ID

  • 12204689

Pubmed Central ID

  • 12204689

Electronic International Standard Serial Number (EISSN)

  • 1879-1301

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/s1074-5521(02)00191-6

Language

  • eng