Rhenium Complexes of Bis(benzothiazole)-Based Tetraarylethylenes as Selective Luminescent Probes for Amyloid Fibrils
Rhenium Complexes of Bis(benzothiazole)-Based Tetraarylethylenes as Selective Luminescent Probes for Amyloid Fibrils
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DOI：
10.1002/chem.201801801
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发表时间：
2018-08-09
影响因子：
4.3
通讯作者：
Pigge, F. Christopher
中科院分区：
文献类型：
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作者：
Gabr, Moustafa T.;Pigge, F. Christopher
用于监测淀粉样蛋白β（Ab）肽聚集的探针对于推进对阿尔茨海默病（AD）的分子发病机制的理解至关重要。在这里，我们报告的发光三羰基化合物的四芳基乙烯（TAE）配体具有双（苯并噻唑）螯合基团与（寡）噻吩单元，已被设计用于监测淀粉样蛋白纤维化的组合。噻吩数量的变化影响了这些复合物的生物物理性质，以及它们对A β（42）原纤维的结合亲和力。所有复合物显示出亚微摩尔的结合A β（42）聚集体的Kd，伴随着高达34倍的增强发光和红移的发射波长。这些复合物的高结合亲和力和理想的生物物理性质使它们成为已建立的荧光A β探针如硫磺素T的潜在替代品。此外，本研究中实施的通用和模块化设计方法应有助于开发第二代基于TAE的诊断工具，用于研究AD和其他神经系统疾病中的蛋白质聚集。
Probes for monitoring aggregation of amyloid beta (Ab) peptides are crucial to advance understanding of the molecular pathogenesis of Alzheimer's Disease (AD). Here, we report luminescent tricarbonyl rhenium complexes of tetraarylethylene (TAE) ligands featuring bis(benzothiazole) chelating groups in combination with (oligo) thiophene units that have been designed for monitoring amyloid fibrillation. Variation in the number of thiophenes influenced the photophysical properties of these complexes, as well as their binding affinities toward A beta(42) fibrils. All complexes displayed submicromolar K-d's for binding A beta(42) aggregates accompanied by up to 34-fold enhanced luminescence and red-shifted emission wavelengths. The high binding affinities and desirable photophysical properties of these complexes render them potential alternatives to established fluorescent A beta probes such as thioflavin T. Additionally, the general and modular design approach implemented in this study should facilitate development of second-generation TAE-based diagnostic tools for studying protein aggregation in AD and other neurological diseases.