title: Recent advances in the discovery of N-myristoyltransferase inhibitors.
abstract: N-Myristoyltransferase (NMT) is a cytosolic monomeric enzyme present in eukaryotes such as fungi and protozoa, but is not found in prokaryotes. The attachment of a 14-carbon saturated fatty acid, myristate, from myristoyl-CoA (14:0 CoA) to the N-terminal glycine residue in a specific set of cellular proteins is commonly called protein N-myristoylation. The myristoylation reaction catalyzed by the enzyme myristoyl CoA:NMT is both necessary for the growth of various organisms and conclusive for cellular proliferation. Therefore, NMT has been identified as a novel and promising target for antifungal, antiparasitic, and anticancer agents, and a large number of potent NMT inhibitors with antifungal, antiparasitic, and anticancer activities have been reported. Herein we describe recent advances in the discovery of NMT inhibitors. We introduce not only the functions of NMT, but also some representative natural and synthetic inhibitors, with a focus on their biological activity, selectivity, and structure-activity relationship (SAR) information. In particular, inspiration from NMT inhibitor structures and the future direction of these compounds are highlighted.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan 250012 (P.R. China), Fax: (+86) 531-88382548.
authors.forename: Can
authors.initials: C
authors.lastname: Zhao
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D010961:Plasmodium / Q000187:drug effects; D013329:Structure-Activity Relationship; D014345:Trypanosoma / Q000187:drug effects; D014352:Trypanosomiasis / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase
keywords: N-myristoyltransferase; anticancer; antifungal; antiparasite; structure-activity relationships