A cell-based assay that targets methionine aminopeptidase in a physiologically relevant environment

Sergio C. Chai, Qi Zhuang Ye

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Methionine aminopeptidase (MetAP) is a promising target for the development of novel antibiotics. However, many potent inhibitors of the purified enzyme failed to show significant antibacterial activity. It is uncertain which divalent metal MetAP uses as its native cofactor in bacterial cells. Herein, we describe a cell-based assay that monitors the hydrolysis of a fluorogenic substrate by overexpressed MetAP in permeabilized Escherichia coli cells and its validation with a set of MetAP inhibitors. This cell-based assay is applicable to those cellular targets with poorly defined native cofactor, increasing the chances of identifying inhibitors that can inhibit the cellular target.

Original languageEnglish (US)
Pages (from-to)2129-2132
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number7
DOIs
StatePublished - Apr 1 2010

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Keywords

  • Antibacterial
  • Cell-based assay
  • Drug screening
  • Enzyme inhibitor
  • Metalloenzyme

ASJC Scopus subject areas

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

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