title: Ghrelin O-acyltransferase assays and inhibition.
abstract: Ghrelin O-acyltransferase (GOAT) is responsible for catalyzing the attachment of the eight-carbon fatty acid octanoyl to the Ser3 side chain of the peptide ghrelin to generate the active form of this metabolic hormone. As such, GOAT is viewed as a potential therapeutic target for the treatment of obesity and diabetes mellitus. Here, we review recent progress in the development of cell and in vitro assays to measure GOAT action and the identification of several synthetic GOAT inhibitors. In particular, we discuss the design, synthesis, and characterization of the bisubstrate analog GO-CoA-Tat and its ability to modulate weight and blood glucose in mice. We also highlight current challenges and future research directions in our biomedical understanding of this fascinating ghrelin processing enzyme.
authors.affiliation: Department of Pharmacology & Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Taylor
authors.forename: Yousang
authors.initials: Y
authors.lastname: Hwang
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Hsiao
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
authors.forename: Philip A
authors.initials: PA
authors.lastname: Cole
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004789:Enzyme Activation; D057075:Enzyme Assays / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054439:Ghrelin / Q000097:blood / Q000737:chemistry*; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D054440:Receptors, Ghrelin / Q000819:agonists / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; C554860:GO-CoA-Tat; D054439:Ghrelin; D008565:Membrane Proteins; D010455:Peptides; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D000217:Acyltransferases; C526983:Mboat4 protein, mouse