St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

ThX-a next-generation probe for the early detection of amyloid aggregates

Thumbnail
View/Open
Needham_2020_CS_ThX_CC.pdf (1.065Mb)
Date
14/05/2020
Author
Needham, Lisa Maria
Weber, Judith
Varela, Juan A.
Fyfe, James W.B.
Do, Dung T.
Xu, Catherine K.
Tutton, Luke
Cliffe, Rachel
Keenlyside, Benjamin
Klenerman, David
Dobson, Christopher M.
Hunter, Christopher A.
Müller, Karin H.
O'Holleran, Kevin
Bohndiek, Sarah E.
Snaddon, Thomas N.
Lee, Steven F.
Keywords
QD Chemistry
Chemistry(all)
DAS
Metadata
Show full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
Abstract
Neurodegenerative diseases such as Alzheimer's and Parkinson's are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, the improved optical properties (extinction coefficient, quantum yield and brightness) of ThX can be used to monitor structural differences in oligomeric species, not observed via traditional ThT imaging.
Citation
Needham , L M , Weber , J , Varela , J A , Fyfe , J W B , Do , D T , Xu , C K , Tutton , L , Cliffe , R , Keenlyside , B , Klenerman , D , Dobson , C M , Hunter , C A , Müller , K H , O'Holleran , K , Bohndiek , S E , Snaddon , T N & Lee , S F 2020 , ' ThX-a next-generation probe for the early detection of amyloid aggregates ' , Chemical Science , vol. 11 , no. 18 , pp. 4578-4583 . https://doi.org/10.1039/c9sc04730a
Publication
Chemical Science
Status
Peer reviewed
DOI
https://doi.org/10.1039/c9sc04730a
ISSN
2041-6520
Type
Journal article
Rights
Copyright © 2020 The Author(s). Open Access article. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Description
Authors thank the Royal Society for the University Research Fellowship of S. F. L. (UF120277). This work was funded in part by the Michael J Fox Foundation and Indiana University. We thank the EPSRC for the Doctoral Prize of L. M. N., J. W, and S. E. B. are funded by Cancer Research UK (C14303/A17197, C47594/A16267), the EPSRC-CRUK Cancer Imaging Centre in Cambridge and Manchester (C197/A16465) and the European Union's Seventh Framework Programme (FP7-PEOPLE-2013- CIG-630729). We thank the European Reseach council for the Starting Grant of J.A.V. (804581).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20177

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter