title: Competitive ABPP of Serine Hydrolases: A Case Study on DAGL-Alpha.
abstract: Competitive activity-based protein profiling is a highly efficient chemical biology technique to determine target engagement and selectivity profiles of enzyme inhibitors in complex proteomes. Fluorophosphonate-based fluorescent inhibitors are widely used as broad-spectrum probes for serine hydrolases. However, diacylglycerol lipase-α is not labeled by fluorophosphonate-based probes. To overcome this problem, we have developed a tailor-made activity-based probe that reacts with diacylglycerol lipase-α. Here we describe a case study in which we apply competitive activity-based protein profiling using a broad-spectrum and a tailor-made activity-based probe to establish selectivity and activity profiles of inhibitors targeting diacylglycerol lipase-α in the mouse brain proteome.
authors: Department of Bio-organic Synthesis, Leiden University, 9500, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. m.p.baggelaar@chem.leidenuniv.nl.
authors: Marc P
authors: MP
authors: Baggelaar
authors: Department of Bio-organic Synthesis, Leiden University, 9500, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. m.van.der.stelt@chem.leidenuniv.nl.
authors: Mario
authors: M
authors: Van der Stelt
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism*; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D020543:Proteome; D012694:Serine / Q000737:chemistry*
chemical_list: D020543:Proteome; D012694:Serine; D006867:Hydrolases; C480280:DAGLA protein, human; D008071:Lipoprotein Lipase
keywords: Competitive ABPP; Diacylglycerol lipase-alpha; Membrane protein; Selectivity profile; Serine hydrolase