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

Organic & Biomolecular Chemistry Pub Date: 2014-09-10 DOI: 10.1039/C4OB01669F

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.

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