| Title : Design and Synthesis of Quenched Activity-based Probes for Diacylglycerol Lipase and alpha,beta-Hydrolase Domain Containing Protein 6 - van Rooden_2018_Chem.Asian.J_13_3491 |
| Author(s) : van Rooden EJ , Kohsiek M , Kreekel R , van Esbroeck ACM , van den Nieuwendijk A , Janssen APA , van den Berg R , Overkleeft HS , van der Stelt M |
| Ref : Chem Asian J , 13 :3491 , 2018 |
| Abstract : Diacylglycerol lipases (DAGL) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol. The fluorescent activity-based probes DH379 and HT-01 have been previously shown to label DAGLs and to cross-react with the serine hydrolase ABHD6. Here, we report the synthesis and characterization of two new quenched activity-based probes 1 and 2, the design of which was based on the structures of DH379 and HT-01, respectively. Probe 1 contains a BODIPY-FL and a 2,4-dinitroaniline moiety as a fluorophore-quencher pair, whereas probe 2 employs a Cy5-fluorophore and a cAB40-quencher. 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-based protein profiling assays using human cell- and mouse brain lysates, but were unfortunately not active in living cells, presumably due to limited cell permeability. |
| ESTHER : van Rooden_2018_Chem.Asian.J_13_3491 |
| PubMedSearch : van Rooden_2018_Chem.Asian.J_13_3491 |
| PubMedID: 29901868 |
van Rooden EJ, Kohsiek M, Kreekel R, van Esbroeck ACM, van den Nieuwendijk A, Janssen APA, van den Berg R, Overkleeft HS, van der Stelt M (2018)
Design and Synthesis of Quenched Activity-based Probes for Diacylglycerol Lipase and alpha,beta-Hydrolase Domain Containing Protein 6
Chem Asian J
13 :3491
van Rooden EJ, Kohsiek M, Kreekel R, van Esbroeck ACM, van den Nieuwendijk A, Janssen APA, van den Berg R, Overkleeft HS, van der Stelt M (2018)
Chem Asian J
13 :3491