单分子阵列检测α -突触核蛋白小分子聚集体

IF 7.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jeff Y. L. Lam, Timothy S. Chisholm, Hadia Almahli, Elizabeth A. English, Zengjie Xia, Yunzhao Wu, Matthew R. Cheetham, Christopher A. Hunter and David Klenerman
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引用次数: 0

摘要

蛋白质聚集体是神经退行性疾病早期诊断的有希望的生物标志物。单分子阵列(SiMoA)是一种检测生物流体中这些超低浓度聚集体的强大方法。在此,我们报告了下一代SiMoA检测方法,使用化学合成的小分子而不是抗体来捕获α -突触核蛋白聚集体,α -突触核蛋白聚集体是帕金森病和其他突触核蛋白病的蛋白质标志。这些基于小分子的捕获剂含有聚集体结合的头基团,以及在SiMoA试验中被伯胺功能化的头缀合的主链。最有希望的分子BF-79-2捕获了微摩尔浓度的重组α -突触核蛋白聚集体,特别是不包括单体。BF-79-2还捕获了人类血液中的α -突触核蛋白聚集体。在SiMoA平台上,用小分子代替抗体作为捕获剂增强了分析的多功能性,因为小分子可以在硅上筛选和合成,而不需要费力的分子生物学技术。小分子作为捕获剂的应用拓宽了SiMoA平台的功能,使其更适合生物标志物的发现和疾病诊断。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Detecting alpha-synuclein aggregates with small molecules on single-molecule array†

Detecting alpha-synuclein aggregates with small molecules on single-molecule array†

Protein aggregates are promising biomarkers for early diagnosis of neurodegenerative disorders. Single-Molecule Array (SiMoA) is a powerful method to detect these aggregates at ultra-low concentrations in biofluids. Herein, we report a next-generation SiMoA assay using chemically synthesized small molecules, rather than antibodies, to capture alpha-synuclein aggregates, a protein hallmark in Parkinson's Disease and other synucleinopathies. These small molecule-based capturing agents contain aggregate-binding head groups, and a backbone functionalized with a primary amine for bead conjugation in the SiMoA assay. The most promising molecule, BF-79-2, captured recombinant alpha-synuclein aggregates, specifically excluding monomers, at picomolar concentrations. BF-79-2 also captured alpha-synuclein aggregates in human blood. Replacing antibodies with small molecules as capturing agents on the SiMoA platform enhances the assay versatility, since small molecules can be screened in silico and synthesized without laborious molecular biology techniques. The application of small molecules as capturing agents broadens the capabilities of the SiMoA platform, rendering it more adaptable for biomarker discovery and disease diagnostics.

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来源期刊
Chemical Science
Chemical Science CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
14.40
自引率
4.80%
发文量
1352
审稿时长
2.1 months
期刊介绍: Chemical Science is a journal that encompasses various disciplines within the chemical sciences. Its scope includes publishing ground-breaking research with significant implications for its respective field, as well as appealing to a wider audience in related areas. To be considered for publication, articles must showcase innovative and original advances in their field of study and be presented in a manner that is understandable to scientists from diverse backgrounds. However, the journal generally does not publish highly specialized research.
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