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Detecting alpha-synuclein aggregates with small molecules on single-molecule array
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DOI：10.1039/D4SC07649D.png)
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Abstract
En 中文
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.
Keywords:
alpha-synuclein aggregates
SiMoA assay
small molecules
biomarker discovery
Parkinson's Disease
Journal
IF:
7.4
Papers:
1.7W
Citations:
9.3W
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