Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis

Molecular Pharmacology & Chemistry Program and Tri-Institutional Research Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 422, New York, NY 10065, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.65). 09/2008; 18(22):5963-6. DOI: 10.1016/j.bmcl.2008.07.130
Source: PubMed

ABSTRACT Menaquinone (vitamin K(2)) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic acid (OSB) during menaquinone biosynthesis. The most potent compound inhibits MenE with an IC(50) value of 5.7microM.

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