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

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.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)