Development of a ribosomal translation system that enables efficient incorporation of nonproteinogenic amino acids
| Project/Area Number |
18H02080
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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 |
Katoh Takayuki 東京大学, 大学院理学系研究科(理学部), 准教授 (90567760)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | ペプチド医薬 / 翻訳 / tRNA / リボソーム / 非天然アミノ酸 / 翻訳合成 / ペプチド創薬 |
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| Outline of Final Research Achievements |
We developed a methodology that enables efficient ribosomal incorporation of nonproteinogenic amino acids, such as D-amino, β-amino, γ-amino, and N-methyl-amino acids, into nascent peptides. By means of this system, we constructed macrocyclic random peptide libraries bearing those nonproteinogenic amino acids and applied them to mRNA display-based in vitro selection against various disease-related target proteins. The obtained macrocyclic peptides exhibited extremely high binding affinity, inhibitory activity, and serum stability.
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| Academic Significance and Societal Importance of the Research Achievements |
D-アミノ酸やβ-アミノ酸、γ-アミノ酸、N-メチルアミノ酸等の非天然アミノ酸はペプチドの安定性や標的への結合力、細胞膜透過性等の特性を向上させることができる。これらの非天然アミノ酸を含む特殊ペプチドの翻訳合成法を確立できれば、鋳型mRNAの配列を変えるだけで容易にランダム特殊ペプチドライブラリを構築することが可能になる。さらに、mRNAディスプレイ法などの配列スクリーニング手法を適用することで、薬理活性を持つ特殊ペプチドを効率的に探索できるため、非常に有効なペプチド創薬プラットフォームとなる。
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] Macrocyclic peptides exhibit antiviral effects against influenza virus HA and prevent pneumonia in animal models2020
Author(s)
Saito, M Itoh Y, Yasui F, Munakata T, Yamane D, Ozawa M, Ito R, Katoh T, Ishigaki H, Nakayama M, Shichinohe S, Yamaji K, Yamamoto N, Ikejiri A, Honda T, Sanada T, Sakoda Y, Kida H, Le TH, Kawaoka Y, Ogasawara Tsukiyama-Kohara T, Suga H, & Kohara M
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Journal Title
Nature Comunications
Volume: -
Issue: 1
Pages: 2654-2654
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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