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

Publication details

The article was received on 16 Jan 2012, accepted on 15 Mar 2012 and first published on 19 Mar 2012


Article type: Concise Article
DOI: 10.1039/C2MD20005H
Med. Chem. Commun., 2012,3, 691-695

  •   Request permissions

    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