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Metabolic disease

GOAT inhibitors to battle the bulge?

Nature Reviews Drug Discovery volume 10, page 22 (2011)Cite this article

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The inhibitor, GO-CoA-Tat, was designed to mimic and 'lock' a putative ternary complex formed between GOAT and its substrates octanoyl-CoA and ghrelin. To achieve this, amino acids 1–10 of ghrelin were linked with a non-cleavable bond to octanoyl-CoA and coupled to an 11-mer HIV Tat-derived sequence to promote membrane permeation.

GO-CoA-Tat specifically and directly interacted with GOAT in cell lines expressing GOAT and pro-ghrelin, and reduced acyl ghrelin formation. Intraperitoneal injection of GO-CoA-Tat in mice fed a high-fat diet resulted in a relative reduction of fat mass, but no difference in lean mass, compared with vehicle-treated or ghrelin-knockout mice. Serum levels of acyl ghrelin, glucose and insulin-like growth factor 1 were reduced, whereas the level of desacyl ghrelin remained unchanged.

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ORIGINAL RESEARCH PAPER

  1. Barnett, B. P. et al. Glucose and weight control in mice with a designed ghrelin O-acetyltransferase inhibitor. Science 18 Nov 2010 (doi:10.1126/science.1196154)

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  1. Alexandra Flemming
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Flemming, A. GOAT inhibitors to battle the bulge?. Nat Rev Drug Discov 10, 22 (2011). https://doi.org/10.1038/nrd3345

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