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Discovery of small molecule vanin inhibitors: new tools to study metabolism and disease.
MedLine Citation:
PMID:  23270378     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Vanins are enzymes with pantetheinase activity and are presumed to play a role in recycling of pantothenic acid (vitamin B5) from pantetheine. Pantothenic acid is an essential nutrient required to synthesize coenzyme A, a cofactor involved in many biological processes such as fatty acid synthesis and oxidation of pyruvate to fuel the citric acid cycle. Hydrolysis of pantetheine also liberates cysteamine, a known antioxidant. Vanin-1 is highly expressed in liver and is under transcriptional control of PPAR-alpha and nutritional status, suggesting a role in energy metabolism. The lack of potent and specific inhibitors of vanins has hampered detailed investigation of their function. We hereby report the design, synthesis and characterization of a novel pantetheine analog, RR6, that acts as a selective, reversible and competitive vanin inhibitor at nanomolar concentration. Oral administration of RR6 in rats completely inhibited plasma vanin activity and caused alterations of plasma lipid concentrations upon fasting, thereby illustrating its potential use in chemical biology research.
Authors:
Patrick A M Jansen; Janna A van Diepen; Bas Ritzen; Patrick L J M Zeeuwen; Ivana Cacciatore; Catia Cornacchia; Ivonne M J J van Vlijmen-Willems; Erik de Heuvel; Peter N M Botman; Richard H Blaauw; Pedro H H Hermkens; Floris P J T Rutjes; Joost Schalkwijk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-27
Journal Detail:
Title:  ACS chemical biology     Volume:  -     ISSN:  1554-8937     ISO Abbreviation:  ACS Chem. Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101282906     Medline TA:  ACS Chem Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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