Chemical proteomics combines chemical biology and mass spectrometry-based proteomics, which is a powerful tool for studying small molecule-protein and protein-protein interactions. In chemical proteomics, synthetic chemical probes react with mechanistically related classes of proteins. The biological function of these proteins can be studied through perturbation or regulation using the probes.
We have developed novel chemical proteomics methods and applying them in biology studies including drug target profiling1,2, nascent protein synthesis3,4 and protein post-translational modifications (PTMs)5. In particular, we have identified the direct-binding protein targets of natural product triptolide, celastrol and withaferin a by combining multiple mass spectrometry-based techniques. We have also developed sulfonyl fluoride-based probes that covalently label a broad swath of the intracellular kinome under physiological condition. We were able to simultaneously identify low-abundant endogenous kinases that bind to clinical kinase inhibitor dasatinib and accurately measure its target engagement rate by mass spectrometry. Based on previous experience, we have also developed “OPP-ID” method for monitoring protein synthesis by using O-propargyl puromycin (OPP) to label newly-synthesized proteins. OPP-ID has been the key technique for us to identify proteins that are synthesized locally in injured sciatic nerve, which has been a key question in Neurobiology.
1.Chemical Science, 2015, 6 (7):4124-4130.
2.Journal of American Chemical Society, 2017, 139 (2):680-685.
3. Proceedings of the National Academy of Sciences. 2018,115 (10) 2353-2358.
4.Science. 2018, 359, 1416-1421.
5. Angewandte Chemie International Edition, 2013, 52 (18):4883–4886.