Identification of α-Synuclein Proaggregator: Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson's Disease.

Authors :: Takada F
Kasahara T
Otake K
Maru T
Miwa M
Muto K
Sasaki M
Hirozane Y
Yoshikawa M
Yamaguchi J
Source :: ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Aug 11; Vol. 13 (9), pp. 1421-1426. Date of Electronic Publication: 2022 Aug 11 (Print Publication: 2022).
Publication Year :: 2022
Abstract: We report the discovery of two compounds, TKD150 and TKD152, that promote the aggregation of α-synuclein (aSN) using a real-time quaking-induced conversion (RT-QuIC) assay to detect abnormal aSN. By utilizing a Pd-catalyzed C-H arylation of benzoxazole with iodoarenes and implementing a planar conformation to the design, we successfully identified TKD150 and TKD152 as proaggregators for aSN. In comparison to a previously reported proaggregator, PA86, the two identified compounds were able to promote aggregation of aSN at twice the rate. Application of TKD150 and TKD152 to the RT-QuIC assay will shorten the inherent lag time and may allow wider use of this assay in clinical settings for the diagnosis of α-synucleinopathy-related diseases.<br />Competing Interests: The authors declare no competing financial interest.<br /> (© 2022 American Chemical Society.)

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