Discovery of Plasmodium Vivax N-myristoyltransferase Inhibitors: Screening, Synthesis, and Structural Characterization of Their Binding Mode

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2012 Mar 24

PMID 22439843

Citations 33

Authors

Victor Goncalves

James A Brannigan

David Whalley

Keith H Ansell

Barbara Saxty

Anthony A Holder

Anthony J Wilkinson

Edward W Tate

Robin J Leatherbarrow

Affiliations

Soon will be listed here.

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.

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