2022 Fiscal Year Final Research Report
Development of bioactive peptides based on molecular design with conformational restriction
| Project/Area Number |
19K06965
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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 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | ペプチド / フォルダマー / 三次元構造制御 / ヘリックス |
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| Outline of Final Research Achievements |
In this study, I aimed to establish a new methodology for bioactive peptide drugs that can target intracellular protein-protein interactions, and I worked on developing functionalized peptides by controlling the three-dimensional structure of the entire molecule. Specifically, I designed peptide foldamers that mimic the spatial arrangement of side-chain functional groups on the α-helix, which is essential for protein-protein interactions. Also, I developed cyclic peptides with high cell membrane permeability by using chiral cyclopropanes with highly controlled conformation as the key unit. As a result, I developed δ-peptide foldamers with an identical 14-helical structure in solution and crystals.
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| Free Research Field |
創薬化学
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| Academic Significance and Societal Importance of the Research Achievements |
ペプチドは新しい創薬モダリティとして注目されている。そのため、タンパク質間相互作用の制御を狙ったペプチドミメティクスの開発研究は盛んになされている。一方で、細胞内の相互作用を標的とした普遍的な方法論といえるものは未だにない。本研究は、細胞内タンパク質間相互作用に適用可能な一般性の高い新規ペプチドミメティクス開発方法論を提示・実践するものである。本研究の成果は、タンパク質間相互作用を標的としたペプチドミメティクス創薬の新たな基盤となりうる。
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