Townsend, D, Hughes, E, Stewart, KL et al. (3 more authors) (2018) Orientation of a Diagnostic Ligand Bound to Macroscopically Aligned Amyloid-ß Fibrils Determined by Solid-state NMR. Journal of Physical Chemistry Letters, 9 (22). pp. 6611-6615. ISSN 1948-7185
Abstract
With amyloid diseases poised to become a major health burden in countries with aging populations, diagnostic molecules that aid the detection of amyloid in vitro and in vivo are of considerable clinical value. Understanding how such ligands recognize their amyloid targets would help to design diagnostics that target specific amyloid types associated with a particular disease, but methods to provide comprehensive information are underdeveloped. Here, solid-state NMR is used to determine the molecular orientation of the amyloid diagnostic 1-fluoro-2,5-bis[(E)-3-carboxy-4-hydroxystyryl]-benzene (FSB) when bound to fibrils of the Alzheimer’s amyloid-β polypeptide aligned on a planar substrate. The 19F NMR spectrum of the aligned complex reveals that FSB is oriented approximately parallel with the fibril long axis and bridges four hydrogen-bonded β-sheets. In addition to providing atomic details to aid the design of amyloid-specific diagnostics, this approach will also illuminate the molecular mechanisms of accessory molecules in amyloid disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry Letters, copyright © 2018 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see [insert ACS Articles on Request author-directed link to Published Work, see https://doi.org/10.1021/acs.jpclett.8b02448 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Structural Molecular Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Nov 2018 14:22 |
Last Modified: | 24 Oct 2019 00:39 |
Status: | Published |
Publisher: | American Chemical Society (ACS) |
Identification Number: | 10.1021/acs.jpclett.8b02448 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138690 |