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Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites

DOI: 10.1039/C4OB01669F DOI Help
PMID: 25230674 PMID Help

Authors: Tayo O. Olaleye (Department of Chemistry, Imperial College London, London, UK) , James A. Brannigan (Structural Biology Laboratory, Department of Chemistry, University of York, York, UK) , Shirley M. Roberts (Structural Biology Laboratory, Department of Chemistry, University of York, York, UK) , Robin J. Leatherbarrow (Department of Chemistry, Imperial College London, London, UK) , Anthony J. Wilkinson (Structural Biology Laboratory, Department of Chemistry, University of York, York, UK) , Edward W. Tate (Department of Chemistry, Imperial College London, London, UK)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Organic & Biomolecular Chemistry , VOL 12 (41) , PAGES 8132-8137

State: Published (Approved)
Published: September 2014
Diamond Proposal Number(s): 7864

Open Access Open Access

Abstract: N-Myristoyltransferase (NMT) has been shown to be essential in Leishmania and subsequently validated as a drug target in Plasmodium. Herein, we discuss the use of antifungal NMT inhibitors as a basis for inhibitor development resulting in the first sub-micromolar peptidomimetic inhibitors of Plasmodium and Leishmania NMTs. High-resolution structures of these inhibitors with Plasmodium and Leishmania NMTs permit a comparative analysis of binding modes, and provide the first crystal structure evidence for a ternary NMT-Coenzyme A/myristoylated peptide product complex.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)