Rational Design of Crystallization Induced Emission Probes to Detect Amorphous Protein Aggregation in Live Cells

Angew Chem Int Ed Engl. 2021 May 14. doi: 10.1002/anie.202103674. Online ahead of print.ABSTRACTUnlike amyloid, amorphous protein aggregation of no defined structures has been challenging to target and detect in complex cellular milieu. Herein, we rationally designed amorphous protein aggregation sensors from aggregation induced emission probes (AIEgens). Utilizing dicyanoisophorone as a model AIEgen scaffold, we first sensitized the fluorescence of AIEgens to non-polar 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 tunes the emission wavelength while retaining selective detection. Finally, we utilized the optimized probe to systematically image aggregated proteome upon proteostasis network regulations. Overall, we present a rational approach to develop amorphous protein aggregation sensors from AIEgens with controllable sensitivity, spectral coverage, and cellular performance.PMID:33991044 | DOI:10.1002/anie.202103674
Source: Angewandte Chemie - Category: Chemistry Authors: Source Type: research