Synthesis and characterization of high affinity fluorogenic α-synuclein probes
Zsofia Lengyel‐Zhand, John J. Ferrie, Bieneke Janssen, Chia‐Ju Hsieh, Thomas J. A. Graham, Kui-ying Xu, Conor M. Haney, Virginia M.‐Y. Lee, John Q. Trojanowski, E. James Petersson, Robert H. Mach
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.