| 研究開始時の研究の概要 |
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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| 研究実績の概要 |
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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