Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase

Sergio C. Chai, Qi Zhuang Ye

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Methionine aminopeptidase (MetAP) plays an essential role for cell survival. Hence, MetAP is a promising target for developing broad spectrum antibacterial agents. MetAP can be activated in vitro by a number of divalent metals, and X-ray structures show that the active site can accommodate two cations. Herein, we demonstrate bacterial growth inhibition by a compound that targets MetAP by recruitment of a third auxiliary metal. Contrary to previous beliefs, this shows that metal-mediated inhibition is a viable approach for discovering MetAP inhibitors that are effective for therapeutic application.

Original languageEnglish (US)
Pages (from-to)6862-6864
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume19
Issue number24
DOIs
StatePublished - Dec 15 2009

Keywords

  • Antibiotics
  • Drug discovery
  • Enzyme inhibitors
  • Metallohydrolase
  • X-ray structure analysis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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