化学
电泳剂
共价键
丙烯酰胺
前药
反应中间体
糖基化
维蒂希反应
活性氧
组合化学
生物化学
立体化学
有机化学
单体
聚合物
受体
催化作用
作者
Ailin Chen,Zih-Jheng Lin,Hung-Tzu Chang,Tsung‐Shing Andrew Wang
摘要
Reactive carbonyl species (RCS) are important biomarkers of oxidative stress-related diseases because of their highly reactive electrophilic nature. Despite their potential as triggers for prodrug activation, selective labeling approaches for RCS remain limited. Here, we utilized triphenylphosphonium groups to chemoselectively capture RCS via an aqueous Wittig reaction, forming α,β-unsaturated carbonyls that enable further functionalization. We first designed native (light) and deuterated (heavy) probes to facilitate RCS metabolomic identification through distinct MS isotope patterns. This approach allowed us to capture and relatively quantify several endogenous RCS related to advanced lipoxidation/glycation end products (ALEs/AGEs). Second, we demonstrated that various endogenous RCS can trigger the in situ generation of acrylamide warheads of targeted covalent inhibitors (TCIs) with different substituents. These structural variations influence their protein binding profiles and consequently alter their cytotoxicity, which is beneficial for the development of inhibitor cocktails.
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