Identification of low-molecular-weight compounds inhibiting growth of corynebacteria: Potential lead compounds for antibiotics

Jaime L. Stark, Jennifer C. Copeland, Alexander Eletsky, Greg A. Somerville, Thomas Szyperski, Robert Powers

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The bacterial genus Corynebacteria contains several pathogenic species that cause diseases such as diphtheria in humans and "cheesy gland" in goats and sheep. Thus, identifying new therapeutic targets to treat Corynebacteria infections is both medically and economically important. CG2496, a functionally uncharacterized protein from Corynebacterium glutamicum, was evaluated using an NMR ligand-affinity screen. A total of 11 compounds from a library of 460 biologically active compounds were shown to selectively bind CG2496 in a highly conserved region of the protein. The best binder was identified to be methiothepin (KD=5419 mm), an FDA-approved serotonin receptor antagonist. Methiothepin was also shown to inhibit the growth of C. glutamicum, but not bacteria that lack CG2496 homologs. Our results suggest that CG2496 is a novel therapeutic target and methiothepin is a potential lead compound or structural scaffold for developing new antibiotics specifically targeting Corynebacteria.

Original languageEnglish (US)
Pages (from-to)282-285
Number of pages4
JournalChemMedChem
Volume9
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Antibiotics
  • Corynebacteria
  • Drug Discovery
  • Fast-Nmr
  • Nmr Spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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