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硫代黄素 T 的结构类似物 DMASEBT 作为研究淀粉样纤维的工具。

Structural Analogue of Thioflavin T, DMASEBT, as a Tool for Amyloid Fibrils Study.

机构信息

Laboratory of Structural Dynamics, Stability and Folding of Proteins , Institute of Cytology of the Russian Academy of Sciences , St. Petersburg 194064 , Russia.

Laboratory of Cell Morphology , Institute of Cytology of the Russian Academy of Sciences , St. Petersburg 194064 , Russia.

出版信息

Anal Chem. 2019 Feb 19;91(4):3131-3140. doi: 10.1021/acs.analchem.8b05737. Epub 2019 Feb 7.

Abstract

Fluorescent dye trans-2-[4-(dimethylamino)styryl]-3-ethyl-1,3-benzothiazolium perchlorate (DMASEBT) is a relatively recently synthesized probe for detection of amyloid fibrils accumulating in the organs and tissues of patients with a wide range of serious incurable diseases. DMASEBT was developed as an alternative of its widely used analogue thioflavin T (ThT), which is the "gold standard" for the amyloid fibrils study. Our results show the similarity of both dyes binding to amyloid fibrils and allow one to propose a mechanism of such probes interaction with some types of the fibrils. At the same time, DMASEBT has a significant advantage, namely, improved photophysical properties compared with ThT, which allows for the detection of DMASEBT-stained amyloid fibrils in the spectral region of the "transparency window of biological tissues". The ability of the dye to penetrate into the cells was shown to open the prospect of this dye's use for amyloid fibrils bioimaging and biosensing in vivo. Furthermore, it was proven that DMASEBT can be used not only as a test for amyloid fibrils formation but also for the comparative study of the fibrils structure (both their fibers and bunches), which in turn may underlie the variability of amyloidosis and affect the cytotoxicity of these protein aggregates.

摘要

荧光染料反式-2-[4-(二甲基氨基)苯乙烯基]-3-乙基-1,3-苯并噻唑翁高氯酸盐(DMASEBT)是一种相对较新合成的探针,用于检测在患有各种严重不治之症的患者的器官和组织中积累的淀粉样纤维。DMASEBT 是其广泛使用的类似物硫代黄素 T(ThT)的替代品,ThT 是淀粉样纤维研究的“金标准”。我们的研究结果表明,两种染料与淀粉样纤维的结合具有相似性,并可以提出这些探针与某些类型纤维相互作用的机制。同时,DMASEBT 具有明显的优势,即与 ThT 相比,其光物理性质得到了改善,这使得可以在生物组织的“透明窗口”光谱区域检测到用 DMASEBT 染色的淀粉样纤维。该染料能够穿透细胞,这为该染料在体内进行淀粉样纤维生物成像和生物传感中的应用开辟了前景。此外,已经证明 DMASEBT 不仅可以用作淀粉样纤维形成的测试,还可以用于对纤维结构(纤维和束)进行比较研究,这反过来又可能是淀粉样变性的变异性的基础,并影响这些蛋白质聚集体的细胞毒性。

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