CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023, China.
The Second Hospital of, Dalian Medical University, 467 Zhongshan Road, Dalian, 116044, China.
Angew Chem Int Ed Engl. 2021 Jul 12;60(29):16067-16076. doi: 10.1002/anie.202103674. Epub 2021 Jun 14.
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.
与淀粉样蛋白聚集物不同，无明确结构的无定形蛋白质聚集物在复杂的细胞环境中难以靶向和检测。在这项研究中，我们从聚集诱导发光探针（AIEgens）中合理设计了无定形蛋白质聚集物的传感器。利用二氰基异佛尔酮作为模型 AIEgen 支架，我们首先将 AIEgens 的荧光敏化到模拟无定形聚集蛋白内部的非极性和粘性环境。我们确定了一个普遍适用的部分（二甲基氨基苯乙烯）用于选择性结合和荧光增强。调节吸电子基团可以调节发射波长，同时保持选择性检测。最后，我们利用优化后的探针系统地在蛋白质稳态网络调节后对聚集蛋白质组进行成像。总的来说，我们提出了一种从 AIEgens 中开发无定形蛋白质聚集物传感器的合理方法，该方法具有可控的灵敏度、光谱覆盖范围和细胞性能。
