Ghrelin O-Acyltransferase Assays and Inhibition

Martin S. Taylor, Yousang Hwang, Po Yuan Hsiao, Jef D. Boeke, Philip A. Cole

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages205-228
Number of pages24
DOIs
StatePublished - Jan 2012

Publication series

NameMethods in Enzymology
Volume514
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • ELISA
  • bisubstrate
  • design
  • inhibitor
  • mechanism
  • metabolism
  • octanoyl-CoA
  • peptide
  • synthetic compound
  • weight

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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