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The fluorescent activity\u2010based probes DH379 and HT\u201001 have been previously shown to label DAGLs and to cross\u2010react with the serine hydrolase ABHD6. Here, we report the synthesis and characterization of two new quenched activity\u2010based probes\u2005<jats:bold>1<\/jats:bold> and <jats:bold>2<\/jats:bold>, the design of which was based on the structures of DH379 and HT\u201001, respectively. Probe\u2005<jats:bold>1<\/jats:bold> contains a BODIPY\u2010FL and a 2,4\u2010dinitroaniline moiety as a fluorophore\u2013quencher pair, whereas probe\u2005<jats:bold>2<\/jats:bold> employs a Cy5\u2010fluorophore and a cAB40\u2010quencher. The fluorescence of both probes was quenched with relative quantum yields of 0.34 and 0.0081, respectively. The probes showed target inhibition as characterized in activity\u2010based protein profiling assays using human cell\u2010 and mouse brain lysates, but were unfortunately not active in living cells, presumably due to limited cell permeability.<\/jats:p>","DOI":"10.1002\/asia.201800452","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T08:37:36Z","timestamp":1528965456000},"page":"3491-3500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Design and Synthesis of Quenched Activity\u2010based Probes for Diacylglycerol Lipase and \u03b1,\u03b2\u2010Hydrolase Domain Containing Protein 6"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0041-6455","authenticated-orcid":false,"given":"E. 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