The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, P. R. China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China.
Anal Chem. 2021 Dec 14;93(49):16447-16455. doi: 10.1021/acs.analchem.1c03401. Epub 2021 Dec 3.
Common solvatochromic fluorophores exhibit a bathochromic fluorescence emission wavelength shift accompanied by intensity attenuation due to the presence of nonradiative decay pathways at the excited state. Such intrinsic but inevitable fluorescence quenching of solvatochromism impedes its applications to faithfully quantify local polarity, especially in a polar environment. Herein, we report a new donor-π-acceptor (D-π-A) type solvatochromic fluorophore scaffold containing a perfluorophenyl group that exhibits both a solvatochromic emission wavelength shift and a controllable emission intensity upon polarity fluctuation. The regulation of fluorescence solvatochromism and colors was achieved by tuning the aryl donors. We exploited such desired solvatochromism of these probes to monitor protein misfolding and aggregation via wavelength shift. Finally, the polarity of pathogenic aggregated proteins was quantified by HaloTag bioorthogonal labeling technology in live cells. While much effort has been devoted to resolving the morphology of pathogenic aggregated proteins, this work provides quantitative hints regarding the chemical information at this disease-related protein interphase.
常见的溶剂变色荧光团由于激发态存在非辐射衰减途径，表现出荧光发射波长红移伴随强度衰减。这种溶剂变色的固有但不可避免的荧光猝灭阻碍了其在准确量化局部极性中的应用，尤其是在极性环境中。在此，我们报告了一种新型的给体-π-受体（D-π-A）型溶剂变色荧光团支架，其中含有一个全氟苯基基团，在极性波动时表现出溶剂变色的发射波长位移和可控制的发射强度。通过调节芳基供体来实现荧光溶剂变色和颜色的调节。我们利用这些探针的理想溶剂变色来通过波长位移监测蛋白质错误折叠和聚集。最后，通过 HaloTag 生物正交标记技术在活细胞中定量致病性聚集蛋白的极性。虽然已经投入大量精力来解析致病性聚集蛋白的形态，但这项工作为与该疾病相关的蛋白质界面的化学信息提供了定量提示。
