Synthesis and characterization of high affinity fluorogenic α-synuclein probes?

Chemical Communications Pub Date: 2020-02-22 DOI: 10.1039/C9CC09849F

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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