| Project/Area Number |
22KF0114
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| Project/Area Number (Other) |
22F22334 (2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
菅 裕明 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
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| Co-Investigator(Kenkyū-buntansha) |
ZHANG YUE 東京大学, 大学院理学系研究科(理学部), 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2024: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2023: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2022: ¥600,000 (Direct Cost: ¥600,000)
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| Keywords | mRNA display / RaPID / peptide drug discovery / peptide cyclization / OPA |
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| Outline of Research at the Start |
We aim to develop OPA-based cyclic peptide libraries using the FIT system. These libraries will selectively release the free reactive moiety after the translation step for peptide cyclization or PTMs, which will be further applied in the RaPID system to identify potential drug molecules. Additionally, we plan to explore a chemoselective peptide cyclization method for post-translational modifications. Through this, we aim to contribute to the development of chemical biology studies and drug discovery efforts, aimed at identifying peptide candidates against various disease-related proteins.
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| Outline of Annual Research Achievements |
We successfully established a thiopeptide/mRNA display platform that enables the de novo discovery of natural product-like thiopeptides with potential bioactivity and high metabolic stability. This powerful selection platform identified a series of thiopeptide candidates with excellent binding affinity and kinase inhibitory activity against a cancer related protein, TNIK. Additionally, the platform was re-engineered to incorporate more nonproteinogenic amino acids, resulting in thiopeptides with significantly improved metabolic stability while maintaining high bioactivity in vitro. These works have been published in J. Am. Chem. Soc., 2024, 146, 12, 8058-8070.; Org. Lett., 2022, 24, 43, 7894-7899.; J. Am. Chem. Soc., 2022, 144 (44), 20332-20341. And we also submitted the patent PCT/JP2023/035472.
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