| Project/Area Number |
18K05334
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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 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 膜タンパク質 / 中分子創薬 / X線結晶構造解析 / クライオ電子顕微鏡単粒子解析 / ファージディスプレイ / 中分子 / 抗体 / 創薬 / 創薬ターゲット / 中分子ペプチド / アロステリックモジュレーター / 阻害剤 |
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| Outline of Final Research Achievements |
Many therapeutic drugs for various diseases such as cancer, hypertension and chronic inflammation target membrane proteins. In this study, I have established a new methodology useful for the creation of medium-sized peptides that regulate the function of medically relevant membrane proteins. In order to validate the technology, we have obtained medium-sized cystein-rich peptides that specifically recognize and bind to several drug-target membrane proteins, such as PD-1, an inhibitory receptor for immune checkpoints, human membrane protein A, which functions as an entry receptor for pathogenic viral infections, and human membrane protein B, which is involved in the acquisition of metastatic potential and progression of malignant transformation in cancer. To elucidate the mode of action of the artificial peptides, I am conducting the structural studies of the membrane protein/medium-sized peptide complexes by cryo-electron microscopy single particle analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、最先端の膜タンパク質構造研究と合成生物学の知見を融合させて中分子創薬に有用なワンストップ技術プラットフォームを創造した点が重要である。研究代表者が既に保有すしていた抗体技術を用いた膜タンパク質構造解析技術の能力を最大限に活用して、取得した中分子アプタマーの結合様式の構造学的検証までを行なった学術的意義と独自性がある。本研究により創出された中分子ペプチドは各種の疾病の治療のための医薬品開発リードとなりうるため、研究成果の社会実装が期待される点からも意義深い。
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