Jump to main content
Jump to site search

Issue 6, 2012
Previous Article Next Article

Mapping of a lipoglycopeptide antibiotic binding site on Staphylococcus aureuspenicillin-binding protein 2 using a vancomycin photoaffinity analogue

Author affiliations

Abstract

Modification of vancomycin with lipophilic substituents enhances its antibacterial activity against vancomycin-resistant strains. To further improve the activity of the resulting lipoglycopeptides, it is necessary to understand these compounds' molecular modes of action. By developing a photoaffinity probe, we were able to elucidate in this study the binding targets of a novel lipoglycopeptide (Van-M-02) at the cell membrane of Staphylococcus aureus. The probe could be successfully used to identify penicillin-binding protein 2 (PBP2), an indispensable enzyme in bacterial cell-wall synthesis, as a target. LC-MS/MS analysis of affinity-labeled PBP2 enabled us to map the Van-M-02 binding site in the transpeptidase domain. These findings will allow for the rational design of better antibiotics against vancomycin-resistant bacteria.

Graphical abstract: Mapping of a lipoglycopeptide antibiotic binding site on Staphylococcus aureus penicillin-binding protein 2 using a vancomycin photoaffinity analogue

Back to tab navigation

Supplementary files

Article information


Submitted
16 Jan 2012
Accepted
15 Mar 2012
First published
19 Mar 2012

Med. Chem. Commun., 2012,3, 691-695
Article type
Concise Article

Mapping of a lipoglycopeptide antibiotic binding site on Staphylococcus aureus penicillin-binding protein 2 using a vancomycin photoaffinity analogue

J. Nakamura, R. Ichikawa, H. Yamashiro, T. Takasawa, X. Wang, Y. Kawai, S. Xu, H. Maki and H. Arimoto, Med. Chem. Commun., 2012, 3, 691
DOI: 10.1039/C2MD20005H

Search articles by author

Spotlight

Advertisements