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

Tayo O. Olaleye, James A. Brannigan, Shirley M. Roberts, Robin J. Leatherbarrow, Anthony J. Wilkinson, Edward W. Tate*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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. This journal is

Original languageEnglish
Pages (from-to)8132-8137
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume12
Issue number41
Early online date10 Sept 2014
DOIs
Publication statusPublished - 7 Nov 2014

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