Chen Jingnan, Wang Yu, Wang Rongtian, Yuan Rujing, Chu Guo-Chao, Li Yi-Ming
School of Food and Biological Engineering, Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, China.
School of Food and Biological Engineering, Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, China.
Bioorg Med Chem Lett. 2023 Oct 1;94:129460. doi: 10.1016/j.bmcl.2023.129460. Epub 2023 Aug 26.
The transiently-activated SUMO probes are conducive to understand the dynamic control of SENPs activity. Here, we developed a photocaged glycine-assisted strategy for the construction of on demand-activated SUMO-ABPs. The light-sensitive groups installed at G and G backbone of SUMO-2 can temporarily block probes activity and hamper aspartimide formation, respectively, which enabled the efficient synthesis of inert SUMO-2 propargylamide (PA). The probe could be activated to capture SENPs upon photo-irradiation not only in vitro but also in intact cells, providing opportunities to further perform intracellular time-resolved proteome-wide profiling of SUMO-related enzymes.
瞬时激活的SUMO探针有助于理解SENPs活性的动态控制。在此，我们开发了一种光笼甘氨酸辅助策略来构建按需激活的SUMO-ABP。安装在SUMO-2的G和G主链上的光敏基团可以分别暂时阻断探针活性并阻碍天冬酰胺的形成，这使得惰性SUMO-2炔丙酰胺（PA）得以高效合成。该探针不仅在体外，而且在完整细胞中经光照射后均可被激活以捕获SENPs，为进一步在细胞内进行SUMO相关酶的时间分辨全蛋白质组分析提供了机会。
