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

Jun Nakamura, Ryota Ichikawa, Hidenori Yamashiro, Takafumi Takasawa, Xaolei Wang, Yasushi Kawai, Shu Xu, Hideki Maki, Hirokazu Arimoto

    Research output: Contribution to journalArticlepeer-review

    1 Citation (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)691-695
    Number of pages5
    JournalMedChemComm
    Volume3
    Issue number6
    DOIs
    Publication statusPublished - 2012 Jun

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Pharmacology
    • Pharmaceutical Science
    • Drug Discovery
    • Organic Chemistry

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