Monday, December 27, 2010
Click chemistry meets Cysteine
How many things happen with it: enzyme activity function, posttranslational modification, crosslinking, redox chemistry, Glutathione, GST the phase II detoxiciation, oxidative stress relief, etc. Everything happens around this unique one amino acid due to its R-SH reactivity.
Benjamin Cravatt and his group at Scripps Research Institute reported a click chemistry approach to obtain a proteome-wide quantitative analysis of native cysteine reactivity, in particular, the identification of hyper-reactive cysteine sites.
The appraoch is termed isoTOP-ABPP (isotopic tandem orthogonal proteolysis–activity-based protein profiling) and shown in the graph. The identified hyper-reactive cysteines correspond well to those of functional and posttranslational modification sites.
Benjamin Cravatt is well known for ABPP and I listened to his talk in Atlanta, 2006. He is one of the pioneers applying click chemistry to chemical biology research. See JACS 2003, 4686. "Activity-Based Protein Profiling in Vivo Using a Copper(I)-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition"
Wonderful walking in the cold air on a Holiday morning - as well as surveying click chemistry progresses with a cup of hot coffee!