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

TY - JOUR

T1 - Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites

AU - Olaleye, Tayo O.

AU - Brannigan, James A.

AU - Roberts, Shirley M.

AU - Leatherbarrow, Robin J.

AU - Wilkinson, Anthony J.

AU - Tate, Edward W.

PY - 2014/11/7

Y1 - 2014/11/7

N2 - 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

AB - 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

UR - http://www.scopus.com/inward/record.url?scp=84907638369&partnerID=8YFLogxK

U2 - 10.1039/c4ob01669f

DO - 10.1039/c4ob01669f

M3 - Article

AN - SCOPUS:84907638369

SN - 1477-0520

VL - 12

SP - 8132

EP - 8137

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 41

ER -