Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.
Journal Article (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
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