Proteome-Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents

Abegg, Daniel; Frei, Reto; Cerato, Luca; Prasad Hari, Durga; Wang, Chao; Waser, Jerome; Adibekian, Alexander (2015). Proteome-Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents Angewandte Chemie International Edition, 54(37), pp. 10852-10857. 10.1002/anie.201505641

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In this study,wepresent ahighly efficient method for proteomic profiling ofcysteine 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 pro- ceeds fast, under mild physiological conditions,and with avery high degree of chemoselectivity.The formed azide-capped alkynyl–cysteine adducts are readily detectable by LC-MS/MS, and can be further functionalizedwith TAMRA or biotin alkyne via CuAAC. We demonstrate the utility of alkynyl benziodoxolones for chemical proteomics applications by identifying the proteomic targets of curcumin, adiarylhepta- noid natural product that was and still is part of multiple human clinical trials as anticancer agent. Our results demon- strate that curcumin covalently modifies several key players of cellular signaling and metabolism, most notably the enzyme casein kinase Igamma. We anticipate that this new method for cysteine profiling will find broad application in chemical proteomics and drug discovery.

Item Type:	Journal Article (Original Article)
Division/Institute:	School of Architecture, Wood and Civil Engineering School of Architecture, Wood and Civil Engineering > Institute for Materials and Wood Technology School of Architecture, Wood and Civil Engineering > AHB Teaching BFH Centres and strategic thematic fields > BFH Centre for Wood - Resource and Material
Name:	Abegg, Daniel; Frei, Reto; Cerato, Luca; Prasad Hari, Durga; Wang, Chao; Waser, Jerome and Adibekian, Alexander
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry R Medicine > R Medicine (General) T Technology > T Technology (General) T Technology > TP Chemical technology
ISSN:	1433-7851
Language:	English
Submitter:	Christelle Ganne-Chédeville
Date Deposited:	21 Apr 2020 10:36
Last Modified:	22 Sep 2021 02:17
Publisher DOI:	10.1002/anie.201505641
URI:	https://arbor.bfh.ch/id/eprint/11286