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Competitive ABPP of Serine Hydrolases: A Case Study on DAGL-Alpha
Marc P Baggelaar1, Mario Van der Stelt2
1Department of Bio-organic Synthesis, Leiden University, 9500, Einsteinweg 55, 2333 CC, Leiden, The Netherlands. m.p.baggelaar@chem.leidenuniv.nl.
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.
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