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

ABSTRACT: 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.

SUBMITTER: Goncalves V

PROVIDER: S-EPMC3863987 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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

Goncalves Victor V Brannigan James A JA Whalley David D Ansell Keith H KH Saxty Barbara B Holder Anthony A AA Wilkinson Anthony J AJ Tate Edward W EW Leatherbarrow Robin J RJ

Journal of medicinal chemistry 20120403 7

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. ...[more]

PMID: 22439843

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