title: Discovery of high affinity inhibitors ofLeishmania donovani N-myristoyltransferase.
abstract: N-Myristoyltransferase (NMT) is a potential drug target inLeishmaniaparasites. Scaffold-hopping from published inhibitors yielded the serendipitous discovery of a chemotype selective forLeishmania donovaniNMT; development led to high affinity inhibitors with excellent ligand efficiency. The binding mode was characterised by crystallography and provides a structural rationale for selectivity.
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Rackham
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Structural Biology Laboratory , Department of Chemistry , University of York , York , YO10 5DD , UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Brannigan
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: William P
authors.initials: WP
authors.lastname: Heal
authors.affiliation: Department of Biology , University of York , York , YO10 5DD , UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paape
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: K Victoria
authors.initials: KV
authors.lastname: Barker
authors.affiliation: Structural Biology Laboratory , Department of Chemistry , University of York , York , YO10 5DD , UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
authors.affiliation: Department of Biology , University of York , York , YO10 5DD , UK.
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leatherbarrow
authors.affiliation: Department of Chemistry , Imperial College London , South Kensington Campus , London , SW7 2AZ , UK . Email: e.tate@imperial.ac.uk ; Tel: +44 (0) 2075 943752.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Tate