Physical Chemistry , ETH Zurich , Vladimir-Prelog-Weg 2 , 8093 Zurich , Switzerland.
Institute of Neuropathology , University Hospital of Zurich, University of Zürich , Schmelzbergstrasse 12 , 8091 Zürich , Switzerland.
ACS Chem Neurosci. 2018 Mar 21;9(3):475-481. doi: 10.1021/acschemneuro.7b00397. Epub 2017 Dec 4.
Luminescent conjugated polythiophenes bind to amyloid proteins with high affinity. Their fluorescence properties, which are modulated by the detailed conformation in the bound state, are highly sensitive to structural features of the amyloid. Polythiophenes therefore represent diagnostic markers for the detection and differentiation of pathological amyloid aggregates. We clarify the binding site and mode of two different polythiophenes to fibrils of the prion domain of the HET-s protein by solid-state NMR and correlate these findings with their fluorescence properties. We demonstrate how amyloid dyes recognize distinct binding sites with specific topological features. Regularly spaced surface charge patterns and well-accessible grooves on the fibril surface define the pharmacophore of the amyloid, which in turn determines the binding mode and fluorescence wavelength of the polythiophene.
发荧光的共轭聚噻吩能高亲和力地与淀粉样蛋白结合。它们的荧光性质受结合状态下的详细构象调制，对淀粉样蛋白的结构特征非常敏感。因此，聚噻吩是用于检测和区分病理淀粉样聚集物的诊断标记物。我们通过固态 NMR 阐明了两种不同的聚噻吩与 HET-s 蛋白的朊病毒结构域的原纤维的结合位点和模式，并将这些发现与它们的荧光性质相关联。我们展示了淀粉样蛋白染料如何识别具有特定拓扑特征的不同结合位点。纤维表面上规则间隔的表面电荷图案和可接近的凹槽定义了淀粉样蛋白的药效团，进而决定了聚噻吩的结合模式和荧光波长。
