Journal
CHEMISTRY-AN ASIAN JOURNAL
Volume 13, Issue 22, Pages 3491-3500Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/asia.201800452
Keywords
activity-based protein profiling; endocannabinoid; enzymes; fluorescent probes; quenched activity-based probes
Categories
Funding
- The Netherlands Organisation for Scientific Research [ECHO-grant] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available