2022 Fiscal Year Final Research Report
Construction of a method to assess and design fibril-forming and/or cytotoxic peptides using short designed peptides
| Project/Area Number |
19K05741
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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 37030:Chemical biology-related
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| Research Institution | Konan University |
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Principal Investigator |
Usui Kenji 甲南大学, フロンティアサイエンス学部, 准教授 (70543792)
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| Co-Investigator(Kenkyū-buntansha) |
梅谷 智弘 甲南大学, 知能情報学部, 准教授 (10397630)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | ペプチド配列 / アミロイド線維 / 細胞毒性 / 細胞接着 / 統計解析 / βシート構造 / 分子記述子 |
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| Outline of Final Research Achievements |
We attempted to find some correlation between sequences and fibril formation and constructing a method to screen fibril forming and cytotoxic sequences from short designed peptides by statistical analysis. In detail, 1) we designed and synthesized short designed peptides. 2) We performed some measurements to evaluate potential of fibril formation. 3) Principal component analysis (PCA) was performed on various combination of the measurement information. 4) We selected the combination that showed the highest cumulative contribution of PC1 and PC2. 5) We selected molecular description used in computational chemistry that has high correlation to PC1 and PC2. 6) We performed cytotoxicity assay. 7) We selected several sequences as candidates with lower cytotoxicity and higher fibril formation based on the two selected molecular descriptors. 8) We synthesized and checked these peptides. This method would be useful tool for screening peptides applying to biomaterials.
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| Free Research Field |
ペプチド工学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではN末端１残基の配列を変更した数十種類の短鎖ペプチドを用い、主成分分析を行うだけで、高い線維化能と低毒性である配列の傾向を予測し、そのような性質を持つ人工官能基を有するペプチド配列の新たな設計に成功した。本研究ではN末端１残基の改変のみにとどまったが、本研究の知見を活かして、配列全体の大幅な改変・設計手法を今後は構築していく。これにより、タンパク質の配列と機能との相関という学術的意義の高い知見の容易な収集・把握が可能となる。本研究で構築した探索法は、今後、ペプチドを生体材料に応用するにあたり、必要かつ有益な情報が得られるツールとして、医療や産業に広く応用展開が期待できる。
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