中国大连化学化学物理研究所刘宇团队报道了一种检测活细胞无定形蛋白聚集的晶化诱导发射探针的合理设计方法。 相关项研究成果发表在2021年5月14日出版的《德国应用化学》。

与淀粉样蛋白不同的是，无定形蛋白聚集在复杂的细胞环境中，对靶向和检测具有挑战性。

该文中，研究人员利用聚集诱导发射探针（AIEgens）合理设计了非晶态蛋白质聚集传感器。利用双氰基异膦酮作为模型AIEgen支架，研究人员首先将AIEgen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中。研究人员确定了一个普遍适用的部分（二甲氨基苯）选择性结合和荧光增强。在保留选择性检测的同时，调节吸电子基团调节发射波长。最后，利用优化后的探针对聚集的蛋白质组进行系统成像。

总的来说，研究人员提出了一种从AIEgens开发具有可控的灵敏度、光谱覆盖范围和细胞性能的非晶形蛋白质聚集传感器的合理方法。

附：英文原文

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

Author: Di Shen, Wenhan Jin, Yulong Bai, Yanan Huang, Haochen Lyu, Lianggang Zeng, Mengdie Wang, Yuqi Tang, Wang Wan, Xuepeng Dong, Zhenming Gao, Hai-Long Piao, Xiaojing Liu, Yu Liu

Issue&Volume: 2021-05-14

Abstract: Unlike 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.

DOI: 10.1002/anie.202103674

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202103674