The thiol-sulfoxonium ylide photo-click reaction for bioconjugation
Chuan Wan, Zhanfeng Hou, Dongyan Yang, Ziyuan Zhou, Hongkun Xu, Yuena Wang, Chuan Dai, Mingchan Liang, Meng Jun, Jiean Chen, Feng Yin, Rui Wang, Zigang Li
Abstract
Visible-light-mediated methods were heavily studied as a useful tool for cysteine-selective bio-conjugation; however, many current methods suffer from bio-incompatible reaction conditions and slow kinetics. To address these challenges, herein, we report a transition metal-free thiol-sulfoxonium ylide photo-click reaction that enables bioconjugation under bio-compatible conditions. The reaction is highly cysteine-selective and generally finished within minutes with naturally occurring riboflavin derivatives as organic photocatalysts. The catalysts and substrates are readily accessible and bench stable and have satisfactory water solubility. As a proof-of-concept study, the reaction was smoothly applied in chemo-proteomic analysis, which provides efficient tools to explore the druggable content of the human proteome.