| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-03-08 |
| タイトル |
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タイトル |
Resveratrol Derivatives Inhibit Transthyretin Fibrillization: Structural Insights into the Interactions between Resveratrol Derivatives and Transthyretin |
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言語 |
en |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| 著者 |
Takeshi Yokoyama
Katsuhiro Kusaka
Mineyuki Mizuguchi
Yuko Nabeshima
Satoru Fujiwara
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Hereditary ATTR amyloidosis is a disease caused by the deposition of amyloid fibrils formed by mutated transthyretin (TTR), a protein that binds to thyroid hormone in the serum, in the organs. The development of a small molecule that binds to and stabilizes TTR is a promising strategy for the treatment of ATTR amyloidosis. In the present study, we demonstrated that the resveratrol derivatives including pterostilbene available as a dietary supplement inhibit the fibrillization of V30M-TTR to the same extent as the approved drug tafamidis. Furthermore, based on a thermodynamic and X-ray crystallographic analysis, the binding of the resveratrol derivative to TTR was shown to be enthalpy-driven, with the binding enthalpy being acquired by hydrogen bonding to S117. Moreover, direct observation of hydrogen atoms by neutron crystallography provided details of the hydrogen bond network by S117 and emphasized the importance of the CH・・・π interaction by L110 in the ligand binding. |
| 書誌情報 |
Journal of Medical Chemistry
巻 66,
号 22,
p. 15511-15523,
発行日 2023-11
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| 出版者 |
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出版者 |
ACS Publications |
| DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1021/acs.jmedchem.3c01698 |
