Rational Design of Crystallization‐Induced‐Emission Probes To Detect Amorphous Protein Aggregation in Live Cells. Issue 29 (14th June 2021)

• Record Type: Journal Article
• Authors: Shen, Di; Jin, Wenhan; Bai, Yulong; Huang, Yanan; Lyu, Haochen; Zeng, Lianggang; Wang, Mengdie; Tang, Yuqi; Wan, Wang; Dong, Xuepeng; Gao, Zhenming; Piao, Hai‐Long; Liu, Xiaojing; Liu, Yu
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 29(2021)
• Page Start: 16067
• Page End: 16076
• Publication Date: 2021-06-14
• Subjects: aggregation-induced emission -- fluorescence -- protein aggregation -- protein homeostasis -- sensors; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202103674
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Unlike amyloid aggregates, amorphous protein aggregates with no defined structures have been challenging to target and detect in a complex cellular milieu. In this study, we rationally designed sensors of amorphous protein aggregation from aggregation‐induced‐emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to a nonpolar and viscous environment mimicking the interior of amorphous aggregated proteins. We identified a generally applicable moiety (dimethylaminophenylene) for selective binding and fluorescence enhancement. Regulation of the electron‐withdrawing groups tuned the emission wavelength while retaining selective detection. Finally, we utilized the optimized probe to systematically image aggregated proteome upon proteostasis network regulation. Overall, we present a rational approach to develop amorphous protein aggregation sensors from AIEgens with controllable sensitivity, spectral coverage, and cellular performance. Abstract : Aggregation‐induced‐emission dyes were rationally designed to detect amorphous protein aggregation with controllable sensitivity, color, and cellular performance (see structure). A dimethylaminophenylene group enabled selective binding and fluorescence enhancement, and the emission wavelength could be tuned by altering the electron‐withdrawing groups on the other ring while retaining selective detection.