Bifunctional fluorescent probes for detection of amyloid aggregates and reactive oxygen species.


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Authors
Needham, Lisa-Maria  ORCID logo  https://orcid.org/0000-0002-8139-5862
Weber, Judith 
Fyfe, James WB 
Kabia, Omaru M 
Do, Dung T 
Abstract

Protein aggregation into amyloid deposits and oxidative stress are key features of many neurodegenerative disorders including Parkinson's and Alzheimer's disease. We report here the creation of four highly sensitive bifunctional fluorescent probes, capable of H2O2 and/or amyloid aggregate detection. These bifunctional sensors use a benzothiazole core for amyloid localization and boronic ester oxidation to specifically detect H2O2. We characterized the optical properties of these probes using both bulk fluorescence measurements and single-aggregate fluorescence imaging, and quantify changes in their fluorescence properties upon addition of amyloid aggregates of α-synuclein and pathophysiological H2O2 concentrations. Our results indicate these new probes will be useful to detect and monitor neurodegenerative disease.

Description
Keywords
ROS, Thioflavin T, fluorophores, protein aggregation, sensors, single-molecule imaging
Journal Title
Royal Society Open Science
Conference Name
Journal ISSN
2054-5703
2054-5703
Volume Title
5
Publisher
Royal Society Publishing
Sponsorship
Cancer Research UK (C14303/A17197)
European Commission (630729)
We 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 The University of Indiana. We thank the EPSRC for the DTA of L.M.N. J.W., Y.Z. and S.E.B. are funded by Cancer Research UK (C14303/A17197, C47594/A16267) and the European Union's Seventh Framework Programme (FP7-PEOPLE-2013-CIG-630729).