Proteome‐Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents. Issue 37 (24th July 2015)

• Record Type: Journal Article
• Authors: Abegg, Daniel; Frei, Reto; Cerato, Luca; Prasad Hari, Durga; Wang, Chao; Waser, Jerome; Adibekian, Alexander
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 37(2015)
• Page Start: 10852
• Page End: 10857
• Publication Date: 2015-07-24
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201505641
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>In this study, we present a highly efficient method for proteomic profiling of cysteine residues in complex proteomes and in living cells. Our method is based on alkynylation of cysteines in complex proteomes using a "clickable" alkynyl benziodoxolone bearing an azide group. This reaction proceeds fast, under mild physiological conditions, and with a very high degree of chemoselectivity. The formed azide‐capped alkynyl–cysteine adducts are readily detectable by LC‐MS/MS, and can be further functionalized with TAMRA or biotin alkyne via CuAAC. We demonstrate the utility of alkynyl benziodoxolones for chemical proteomics applications by identifying the proteomic targets of curcumin, a diarylheptanoid natural product that was and still is part of multiple human clinical trials as anticancer agent. Our results demonstrate that curcumin covalently modifies several key players of cellular signaling and metabolism, most notably the enzyme casein kinase I gamma. We anticipate that this new method for cysteine profiling will find broad application in chemical proteomics and drug discovery.</p> </abstract>