Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity

Peter I. O'Daniel, Zhihong Peng, Hualiang Pi, Sebastian A. Testero, Derong Ding, Edward Spink, Erika Leemans, Marc A. Boudreau, Takao Yamaguchi, Valerie A. Schroeder, William R. Wolter, Leticia I. Llarrull, Wei Song, Elena Lastochkin, Malika Kumarasiri, Nuno T. Antunes, Mana Espahbodi, Katerina Lichtenwalter, Mark A. Suckow, Sergei VakulenkoShahriar Mobashery, Mayland Chang

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.

Original languageEnglish
Pages (from-to)3664-3672
Number of pages9
JournalJournal of the American Chemical Society
Volume136
Issue number9
DOIs
StatePublished - Mar 5 2014

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity'. Together they form a unique fingerprint.

Cite this