title: A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups.
abstract: Inhibitors of ghrelin O-acyltransferase (GOAT) have untapped potential as therapeutics targeting obesity and diabetes. We report the first examples of GOAT inhibitors incorporating a triazole linkage as a biostable isosteric replacement for the ester bond in ghrelin and amide bonds in previously reported GOAT inhibitors. These triazole-containing inhibitors exhibit sub-micromolar inhibition of the human isoform of GOAT (hGOAT), and provide a foundation for rapid future chemical diversification and optimization of hGOAT inhibitors.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Darling
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA. Electronic address: hougland@syr.edu.
authors.forename: James L
authors.initials: JL
authors.lastname: Hougland
mesh_terms: D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D014230:Triazoles; D000217:Acyltransferases; C542776:MBOAT4 protein, human
keywords: 1,2,3-Triazole; Ghrelin; Ghrelin O-acyltransferase; Peptidomimetic; Serine acylation