Yang Jing
Guangzhou National Laboratory, Guangzhou International Bio-Island Guangzhou China
School of Pharmaceutical Sciences, Guangzhou Medical University Guangzhou China.
Chem Sci. 2025 Apr 24. doi: 10.1039/d5sc02016f.
Cysteine sulfenic acid (SOH) modifications are pivotal in redox signaling, yet establishing their causal biological roles remains challenging due to methodological limitations. Traditional approaches often lack precision or disrupt non-redox cysteine functions. This perspective highlights two innovative chemical biology strategies to address these challenges: (1) integrating bioorthogonal cleavage chemistry with genetic code expansion for site-specific SOH incorporation in proteins of interest, enabling controlled activation of redox events, and (2) developing redox-targeted covalent inhibitors (TCIs) to selectively block SOH modifications. By bridging technological innovation with mechanistic inquiry, these strategies not only help elucidate SOH-mediated signaling networks for a better understanding of redox biology, but also hold therapeutic promise for precise redox medicine.
半胱氨酸亚磺酸（SOH）修饰在氧化还原信号传导中起关键作用，但由于方法学上的局限性，确定其因果生物学作用仍然具有挑战性。传统方法往往缺乏精确性或会破坏非氧化还原半胱氨酸的功能。本文观点强调了两种创新的化学生物学策略来应对这些挑战：（1）将生物正交切割化学与遗传密码扩展相结合，以在目标蛋白中进行位点特异性SOH掺入，从而实现对氧化还原事件的可控激活；（2）开发氧化还原靶向共价抑制剂（TCI）以选择性阻断SOH修饰。通过将技术创新与机制探究相结合，这些策略不仅有助于阐明SOH介导的信号网络，以更好地理解氧化还原生物学，而且在精准氧化还原医学方面也具有治疗前景。
