2021 Fiscal Year Final Research Report
Molecular design of non-steroidal ecdysone-like compounds
| Project/Area Number |
19K06051
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 39040:Plant protection science-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | ecdysone / ecdysone receptor / dibenzoylhydrazine / in silico screening / receptor binding / molting hormone |
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| Outline of Final Research Achievements |
It is known that the binding sites of natural steroid hormones to the molting hormone receptor differ from those of dibenzoylhydrazine and imidazole derivatives, which are non-steroidal compounds. In this study, we aimed to find non-steroidal compounds that are active against all insects by searching for compounds that can bind to the binding sites of natural steroidal hormones such as 20-hydroxyecdysone and ponasterone A. In this study the software for in silico screening was used to find new compounds. To obtain the information for the ligand binding to the receptor, the molecular dynamics and the binding energy calculation were performed. Here, the binding free energy of compounds were positively correlated with their receptor binding. This result will be useful for the future in silico screening.
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| Free Research Field |
生物調節化学
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| Academic Significance and Societal Importance of the Research Achievements |
ステロイド型の脱皮ホルモン誘導体の活性を定量的に調べ，さらにリガンドー受容体結合エネルギーとの間に正の相関関係を見出した．このことは，インシリコスクリーニングの精度の上昇に繋がるとともに，他の受容体結合親和性リガンドの探索にとっても有用な結果をもたらす．500万化合物の構造データーベースを用いて，インシリコスクリーニングを行い，そこから，脱皮ホルモン受容体に結合可能な候補化合物を見出した．その化合物の結合親和性は天然の脱皮ホルモンの親和性に比べて，活性の低いものであったが，構造展開を行って活性を上昇させることができた．さらに結合親和性を上げることにより，殺虫性化合物を見出すことができる．
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