Department of Chemistry, University of Iowa, Iowa City, IA, 52242, USA.
Chemistry. 2018 Aug 9;24(45):11729-11737. doi: 10.1002/chem.201801801. Epub 2018 Jul 9.
Probes for monitoring aggregation of amyloid beta (Aβ) 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 Aβ fibrils. All complexes displayed submicromolar K for binding Aβ 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 Aβ 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.
用于监测淀粉样β(Aβ)肽聚集的探针对于深入了解阿尔茨海默病(AD)的分子发病机制至关重要。在这里,我们报告了四芳基乙烯(TAE)配体的三羰基铼配合物,其特征是具有双(苯并噻唑)螯合基团和(齐聚)噻吩单元,这些单元旨在监测淀粉样纤维形成。噻吩数量的变化影响了这些配合物的光物理性质,以及它们与 Aβ纤维的结合亲和力。所有配合物对 Aβ聚集物的结合均显示出亚微摩尔 K 值,同时伴有高达 34 倍的增强发光和发射波长红移。这些配合物具有高结合亲和力和理想的光物理性质,因此可能成为噻唑啉 T 等已建立的荧光 Aβ探针的替代品。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基于 TAE 的第二代诊断工具,用于研究 AD 和其他神经疾病中的蛋白质聚集。