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Issue 24, 2020
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Synthesis and characterization of high affinity fluorogenic α-synuclein probes

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Abstract

Fluorescent small molecules are powerful tools for imaging α-synuclein pathology in vitro and in vivo. In this work, we explore benzofuranone as a potential scaffold for the design of fluorescent α-synuclein probes. These compounds have high affinity for α-synuclein, show fluorescent turn-on upon binding to fibrils, and display different binding to Lewy bodies, Lewy neurites and glial cytoplasmic inclusion pathologies in post-mortem brain tissue. These studies not only reveal the potential of benzofuranone compounds as α-synuclein specific fluorescent probes, but also have implications for the ways in which α-synucleinopathies are conformationally different and display distinct small molecule binding sites.

Graphical abstract: Synthesis and characterization of high affinity fluorogenic α-synuclein probes

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Supplementary files

Article information


Submitted
19 Dec 2019
Accepted
20 Feb 2020
First published
22 Feb 2020

Chem. Commun., 2020,56, 3567-3570
Article type
Communication

Synthesis and characterization of high affinity fluorogenic α-synuclein probes

Z. Lengyel-Zhand, J. J. Ferrie, B. Janssen, C. Hsieh, T. Graham, K. Xu, C. M. Haney, V. M.-Y. Lee, J. Q. Trojanowski, E. J. Petersson and R. H. Mach, Chem. Commun., 2020, 56, 3567
DOI: 10.1039/C9CC09849F

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