A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups

Feifei Zhao; Joseph E. Darling; Richard A. Gibbs; James L. Hougland

doi:10.1016/j.bmcl.2015.05.009

A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups

Feifei Zhao, Joseph E. Darling, Richard A. Gibbs, James L. Hougland

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2800-2803
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2015.05.009
State	Published - Jun 4 2015

Keywords

1,2,3-Triazole
Ghrelin
Ghrelin O-acyltransferase
Peptidomimetic
Serine acylation

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2015.05.009

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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.",

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T1 - A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups

AU - Zhao, Feifei

AU - Darling, Joseph E.

AU - Gibbs, Richard A.

AU - Hougland, James L.

PY - 2015/6/4

Y1 - 2015/6/4

N2 - 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.

AB - 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.

KW - 1,2,3-Triazole

KW - Ghrelin

KW - Ghrelin O-acyltransferase

KW - Peptidomimetic

KW - Serine acylation

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A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups

Abstract

Keywords

ASJC Scopus subject areas

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