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Synthesis and characterization of high affinity fluorogenic α-synuclein probes.
Chemical Communications ( IF 6.164 ) Pub Date : 2020-02-27 , DOI: 10.1039/c9cc09849f
Zsofia Lengyel-Zhand,John J Ferrie,Bieneke Janssen,Chia-Ju Hsieh,Thomas Graham,Kui-Ying Xu,Conor M Haney,Virginia M-Y Lee,John Q Trojanowski,E James Petersson,Robert H Mach

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.
更新日期:2020-03-26

 

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