Extended targeting potential and improved synthesis of Microcin C analogs as antibacterials

Gaston H.M. Vondenhoff, Svetlana Dubiley, Konstantin Severinov, Eveline Lescrinier, Jef Rozenski, Arthur Van Aerschot

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Microcin C (McC) (1) is a potent antibacterial compound produced by some Escherichia coli strains. McC functions through a Trojan-Horse mechanism: it is actively taken up inside a sensitive cell through the function of the YejABEF-transporter and then processed by cellular aminopeptidases. Processed McC (2) is a non-hydrolysable aspartyl-adenylate analog that inhibits aspartyl-tRNA synthetase (AspRS). A new synthesis is described that allows for the production of a wide variety of McC analogs in acceptable amounts. Using this synthesis a number of diverse compounds was synthesized with altered target specificity. Further characteristics of the YejABEF transporters were determined using these compounds.

Original languageEnglish (US)
Pages (from-to)5462-5467
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number18
DOIs
StatePublished - Sep 15 2011

All Science Journal Classification (ASJC) codes

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

Keywords

  • Antibiotics
  • Drug design
  • Microcin C analogs

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