CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Chembiochem. 2022 Feb 16;23(4):e202100443. doi: 10.1002/cbic.202100443. Epub 2021 Oct 15.
Protein misfolding and aggregation is a complex biochemical process and has been associated with numerous human degenerative diseases. Developing novel chemical and biological tools and approaches to visualize aggregated proteins in live cells is in high demand for mechanistic studies, diagnostics, and therapeutics. In this review, we summarize the recent developments in the chemical biology toolbox applied to protein aggregation studies in live cells. These methods exploited fluorescent protein tags, fluorescent chemical tags, and small-molecule probes to visualize the protein-aggregation process, detect proteome stresses, and quantify the protein homeostasis network capacity. Inspired by these seminal works, we have generalized design principles for the development of new detection methods and probes in the future that will illuminate this important biological process.
蛋白质错误折叠和聚集是一个复杂的生化过程，与许多人类退行性疾病有关。开发新的化学和生物学工具以及方法来可视化活细胞中的聚集蛋白，这对于机制研究、诊断和治疗都有很高的需求。在这篇综述中，我们总结了应用于活细胞中蛋白质聚集研究的化学生物学工具包的最新进展。这些方法利用荧光蛋白标签、荧光化学标签和小分子探针来可视化蛋白质聚集过程、检测蛋白质组应激和量化蛋白质动态平衡网络的能力。受这些开创性工作的启发，我们总结了设计用于开发新的检测方法和探针的通用设计原则，这些方法将为这个重要的生物学过程提供更多的见解。
