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.
Chemistry. 2021 Oct 21;27(59):14564-14576. doi: 10.1002/chem.202102344. Epub 2021 Sep 16.
Protein phase separation process involving protein unfolding, misfolding, condensation and aggregation etc. has been associated with numerous human degenerative diseases. The complexity in protein conformational transitions results in multi-step and multi-species biochemical pathways upon protein phase separation. Recent progresses in designing novel fluorescent probes have unraveled the enriched details of phase separated proteins and provided mechanistic insights towards disease pathology. In this review, we summarized the design and characterizations of fluorescent probes that selectively illuminated proteins at different phase separated states with a focus on aggregation-induced emission probes, fluorescent molecular rotors, and solvatochromic fluorophores. Inspired by these pioneering works, a design blueprint was proposed to further develop fluorescent probes that can potentially shed light on the unresolved protein phase separated states in the future.
蛋白质相分离过程涉及蛋白质的展开、错误折叠、凝聚和聚集等，与许多人类退行性疾病有关。蛋白质构象转变的复杂性导致蛋白质相分离后的多步骤和多物种生化途径。设计新型荧光探针的最新进展揭示了相分离蛋白质的丰富细节，并为疾病病理学提供了机制见解。在这篇综述中，我们总结了选择性照亮不同相分离状态蛋白质的荧光探针的设计和特性，重点介绍了聚集诱导发射探针、荧光分子转子和溶剂化荧光团。受这些开创性工作的启发，提出了一个设计蓝图，以进一步开发荧光探针，这些探针有可能在未来揭示未解决的蛋白质相分离状态。
