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Structure-Based Design of Potent and Selective Leishmania N-Myristoyltransferase Inhibitors

Hutton, JA, Goncalves, V, Brannigan, JA, Paape, D, Wright, MH, Waugh, TM, Roberts, SM, Bell, AS, Wilkinson, AJ, Smith, DF, Leatherbarrow, RJ and Tate, EW (2014) Structure-Based Design of Potent and Selective Leishmania N-Myristoyltransferase Inhibitors. Journal of Medicinal Chemistry, 57 (20). pp. 8664-8670. ISSN 0022-2623

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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 Leishmania donovani NMT inhibitors with good selectivity over the human enzyme.

Item Type: Article
Uncontrolled Keywords: 0304 Medicinal And Biomolecular Chemistry, 1115 Pharmacology And Pharmaceutical Sciences, 0305 Organic Chemistry
Subjects: Q Science > QD Chemistry
Q Science > QR Microbiology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Vice-Chancellor's Office
Publisher: American Chemical Society
Related URLs:
Date Deposited: 20 Jun 2018 09:35
Last Modified: 04 Sep 2021 10:25
DOI or ID number: 10.1021/jm5011397
URI: https://researchonline.ljmu.ac.uk/id/eprint/8770
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