Triphenylphosphonium ylides, known as Wittig reagents, are one of the most commonly used tools in synthetic chemistry. Despite their considerable versatility, Wittig reagents have not yet been explored for their utility in biological applications. Here we introduce a chemoselective ligation reaction that harnesses the reactivity of Wittig reagents and the unique chemical properties of sulfenic acid, a pivotal post-translational cysteine modification in redox biology. The reaction, which generates a covalent bond between the ylide nucleophilic α-carbon and electrophilic γ-sulfur, is highly selective, rapid and affords robust labelling under a range of biocompatible reaction conditions, which includes in living cells. We highlight the broad utility of this conjugation method to enable site-specific proteome-wide stoichiometry analysis of S-sulfenylation and to visualize redox-dependent changes in mitochondrial cysteine oxidation and redox-triggered triphenylphosphonium generation for the controlled delivery of small molecules to mitochondria.

三苯基鏻叶立德，被称为 Wittig 试剂，是合成化学中最常用的工具之一。尽管 Wittig 试剂具有相当多的多功能性，但尚未探索其在生物应用中的效用。在这里，我们介绍了一种化学选择性连接反应，该反应利用了 Wittig 试剂的反应性和亚磺酸的独特化学性质，亚磺酸是氧化还原生物学中关键的翻译后半胱氨酸修饰。该反应在叶立德亲核 α-碳和亲电子 γ-硫之间产生共价键，具有高度选择性、快速性，并在包括活细胞在内的一系列生物相容性反应条件下提供稳健的标记。我们强调了这种缀合方法的广泛用途，以实现对位点特异性蛋白质组范围的化学计量分析S-亚磺酰化并可视化线粒体半胱氨酸氧化和氧化还原触发的三苯基鏻生成中的氧化还原依赖性变化，以控制小分子向线粒体的传递。