Electron‐withdrawing inductive effects enhanced strategy for protein thiol sensing and blocking agent design

Abstract It is a great challenge to discover novel chemical reactions suitable for biological analysis in a living system. The development of novel protein thiol blocking agents is a crucial need for exploring protein thiol functions in protein refolding, signal transduction, and redox regulation. We are always keen on seeking novel chemical reactions applied to endogenous biological macromolecules or protein thiol sensing, blocking, and labeling. In the present work, we have successfully developed a novel agent to block protein thiol by enhanced electron‐withdrawing inductive effects. This sensing and blocking process was detailedly monitored by UV‐vis, fluorescent spectra, and SDS‐Page gel separation. The spectral studies demonstrated that the agent could react ultrafastly with thiol within seconds at μM level. Furthermore, fluorescent imaging in cells and in vivo was further used for the validation of its ability to sensing and blocking thiol, providing evidence of downregulated protein thiols in Parkinson's disease. The enhanced electron‐withdrawing inductive effect strategy in this work may provide a general guideline for designing protein thiol agent.