期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 29, 页码 16067-16076出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202103674
关键词
aggregation-induced emission; fluorescence; protein aggregation; protein homeostasis; sensors
资金
- National Natural Science Foundation of China [21907091]
- LiaoNing Revitalization Talents Program from the Liaoning province of China [XLYC1907048]
- China Postdoctoral Science Foundation [2019M661138]
- Dalian Innovation Fund [2020JJ26GX027]
- Pfizer
- Taishan Scholars Project of Shandong Province [tsqn201909017]
This study developed sensors for amorphous protein aggregation from aggregation-induced-emission probes (AIEgens) with controllable sensitivity, spectral coverage, and cellular performance through rational design.
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.
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