Discovery of Plasmodium vivax N-myristoyltransferase inhibitors: screening, synthesis, and structural characterization of their binding mode

TY - JOUR

T1 - Discovery of Plasmodium vivax N-myristoyltransferase inhibitors

T2 - screening, synthesis, and structural characterization of their binding mode

AU - Goncalves, Victor

AU - Brannigan, James A

AU - Whalley, David

AU - Ansell, Keith H

AU - Saxty, Barbara

AU - Holder, Anthony A

AU - Wilkinson, Anthony J

AU - Tate, Edward W

AU - Leatherbarrow, Robin J

N1 - © 2012 American Chemical Society

PY - 2012/4/12

Y1 - 2012/4/12

N2 - N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the chemical groups relevant for activity and selectivity.

AB - N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the chemical groups relevant for activity and selectivity.

UR - http://www.scopus.com/inward/record.url?scp=84859790956&partnerID=8YFLogxK

U2 - 10.1021/jm300040p

DO - 10.1021/jm300040p

M3 - Article

C2 - 22439843

VL - 55

SP - 3578

EP - 3582

JO - JOURNAL OF MEDICINAL CHEMISTRY

JF - JOURNAL OF MEDICINAL CHEMISTRY

IS - 7

ER -