Cargando…
Identification of α-Synuclein Proaggregator: Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s Disease
[Image: see text] 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 implement...
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2022
|
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465709/ https://www.ncbi.nlm.nih.gov/pubmed/36105342 http://dx.doi.org/10.1021/acsmedchemlett.2c00138 |
| _version_ | 1784787858567987200 |
|---|---|
| author | Takada, Fumito Kasahara, Takahito Otake, Kentaro Maru, Takamitsu Miwa, Masanori Muto, Kei Sasaki, Minoru Hirozane, Yoshihiko Yoshikawa, Masato Yamaguchi, Junichiro |
| author_facet | Takada, Fumito Kasahara, Takahito Otake, Kentaro Maru, Takamitsu Miwa, Masanori Muto, Kei Sasaki, Minoru Hirozane, Yoshihiko Yoshikawa, Masato Yamaguchi, Junichiro |
| author_sort | Takada, Fumito |
| collection | PubMed |
| description | [Image: see text] 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. |
| format | Online Article Text |
| id | pubmed-9465709 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-94657092022-09-13 Identification of α-Synuclein Proaggregator: Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s Disease Takada, Fumito Kasahara, Takahito Otake, Kentaro Maru, Takamitsu Miwa, Masanori Muto, Kei Sasaki, Minoru Hirozane, Yoshihiko Yoshikawa, Masato Yamaguchi, Junichiro ACS Med Chem Lett [Image: see text] 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. American Chemical Society 2022-08-11 /pmc/articles/PMC9465709/ /pubmed/36105342 http://dx.doi.org/10.1021/acsmedchemlett.2c00138 Text en © 2022 American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
| spellingShingle | Takada, Fumito Kasahara, Takahito Otake, Kentaro Maru, Takamitsu Miwa, Masanori Muto, Kei Sasaki, Minoru Hirozane, Yoshihiko Yoshikawa, Masato Yamaguchi, Junichiro Identification of α-Synuclein Proaggregator: Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s Disease |
| title | Identification
of α-Synuclein Proaggregator:
Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s
Disease |
| title_full | Identification
of α-Synuclein Proaggregator:
Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s
Disease |
| title_fullStr | Identification
of α-Synuclein Proaggregator:
Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s
Disease |
| title_full_unstemmed | Identification
of α-Synuclein Proaggregator:
Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s
Disease |
| title_short | Identification
of α-Synuclein Proaggregator:
Rapid Synthesis and Streamlining RT-QuIC Assays in Parkinson’s
Disease |
| title_sort | identification
of α-synuclein proaggregator:
rapid synthesis and streamlining rt-quic assays in parkinson’s
disease |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465709/ https://www.ncbi.nlm.nih.gov/pubmed/36105342 http://dx.doi.org/10.1021/acsmedchemlett.2c00138 |
| work_keys_str_mv | AT takadafumito identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT kasaharatakahito identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT otakekentaro identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT marutakamitsu identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT miwamasanori identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT mutokei identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT sasakiminoru identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT hirozaneyoshihiko identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT yoshikawamasato identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease AT yamaguchijunichiro identificationofasynucleinproaggregatorrapidsynthesisandstreamliningrtquicassaysinparkinsonsdisease |