Electrophilic Sulfonium-Promoted Peptide and Protein Amidation in Aqueous Media

A novel amidation strategy using electrophilic sulfonium, which is soluble and stable in aqueous conditions, was developed. The sulfoniums could activate thioacid and carboxyl acid to efficiently react with amines to afford amides. This method enables applications in amidation in both aqueous media and solid-phase peptide synthesis, peptide/protein modifications, and reactive lysines of a proteome at pH 10 with activity-based protein profiling. A peptide ligand-directed labeling of the USP7–UBL2 domain was also performed using this method.本研究开发了一种基于亲电锍盐（electrophilic sulfonium）的新型酰胺化策略，该类锍盐在水相环境中具备良好溶解性与稳定性。该锍盐可活化硫代酸（thioacid）与羧酸（carboxyl acid），使其能与胺类高效反应生成酰胺。该策略可应用于多类场景：包括水相介质中的酰胺化反应、固相肽合成（solid-phase peptide synthesis）、肽/蛋白质修饰，以及在pH 10条件下借助基于活性的蛋白质谱分析（activity-based protein profiling）实现蛋白质组反应性赖氨酸标记。此外，本方法还被用于USP7–UBL2结构域（USP7–UBL2 domain）的肽配体导向标记实验。