Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8503, Japan.
Org Biomol Chem. 2018 Aug 29;16(34):6168-6179. doi: 10.1039/c8ob01484a.
Reactive oxygen species (ROS) and radical species generated using oxidative single-electron transfer (SET) catalysts are highly reactive, inducing local environmental oxidative reactions, resulting in protein inactivation and labelling in proximity to the catalysts. Oxidative catalysts bound to the target protein generate ROS which induce oxidation only within a limited radius (∼30 nm), resulting in target-protein-selective inactivation. On the other hand, protein chemical labelling reactions via ROS or SET induced by the catalysts are completed in proximity to the catalyst. These proximity labelling techniques have recently attracted considerable attention as innovative tools to elucidate protein interaction mapping and unknown protein-protein interaction (PPI) partners. Not only can peroxidases be genetically introduced into the protein of interest but also ligand-conjugated catalysts can catalyze oxidative SET reactions in a protein mixture under intracellular conditions. In this review, we focus on two approaches of selective inactivation of protein functions and selective protein labelling using oxidative SET catalysts.
活性氧(ROS)和自由基是通过氧化单电子转移(SET)催化剂产生的,具有高度的反应活性,诱导局部环境氧化反应,导致邻近催化剂的蛋白质失活和标记。与靶蛋白结合的氧化催化剂产生 ROS,仅在有限的半径(约 30nm)内诱导氧化,导致靶蛋白选择性失活。另一方面,通过催化剂诱导的 ROS 或 SET 进行的蛋白质化学标记反应在催化剂附近完成。这些邻近标记技术最近作为创新工具引起了相当大的关注,可用于阐明蛋白质相互作用图谱和未知蛋白质-蛋白质相互作用(PPI)伙伴。不仅可以将过氧化物酶遗传引入到感兴趣的蛋白质中,而且配体缀合的催化剂还可以在细胞内条件下催化蛋白质混合物中的氧化 SET 反应。在这篇综述中,我们重点介绍了使用氧化 SET 催化剂选择性失活蛋白质功能和选择性蛋白质标记的两种方法。