Rodrigues, M, Bhattacharjee, P, Brinkmalm, A et al. (17 more authors) (2022) Structure-specific amyloid precipitation in biofluids. Nature Chemistry, 14 (9). pp. 1045-1053. ISSN 1755-4330
Abstract
The composition of soluble toxic protein aggregates formed in vivo is currently unknown in neurodegenerative diseases, due to their ultra-low concentration in human biofluids and their high degree of heterogeneity. Here we report a method to capture amyloid-containing aggregates in human biofluids in an unbiased way, a process we name amyloid precipitation. We use a structure-specific chemical dimer, a Y-shaped, bio-inspired small molecule with two capture groups, for amyloid precipitation to increase affinity. Our capture molecule for amyloid precipitation (CAP-1) consists of a derivative of Pittsburgh Compound B (dimer) to target the cross β-sheets of amyloids and a biotin moiety for surface immobilization. By coupling CAP-1 to magnetic beads, we demonstrate that we can target the amyloid structure of all protein aggregates present in human cerebrospinal fluid, isolate them for analysis and then characterize them using single-molecule fluorescence imaging and mass spectrometry. Amyloid precipitation enables unbiased determination of the molecular composition and structural features of the in vivo aggregates formed in neurodegenerative diseases.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022, The Author(s), under exclusive licence to Springer Nature Limited. This is an author produced version of an article published in Nature Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Dec 2022 16:26 |
Last Modified: | 07 Jan 2023 01:13 |
Status: | Published |
Publisher: | Nature Research |
Identification Number: | 10.1038/s41557-022-00976-3 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:193796 |