Ontology highlight
ABSTRACT:
SUBMITTER: Hutton JA
PROVIDER: S-EPMC4211304 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Hutton Jennie A JA Goncalves Victor V Brannigan James A JA Paape Daniel D Wright Megan H MH Waugh Thomas M TM Roberts Shirley M SM Bell Andrew S AS Wilkinson Anthony J AJ Smith Deborah F DF Leatherbarrow Robin J RJ Tate Edward W EW
Journal of medicinal chemistry 20141001 20
Inhibitors of Leishmania N-myristoyltransferase (NMT), a potential target for the treatment of leishmaniasis, obtained from a high-throughput screen, were resynthesized to validate activity. Crystal structures bound to Leishmania major NMT were obtained, and the active diastereoisomer of one of the inhibitors was identified. On the basis of structural insights, enzyme inhibition was increased 40-fold through hybridization of two distinct binding modes, resulting in novel, highly potent Leishmani ...[more]