2020 Fiscal Year Final Research Report
Triazole-linked aminoacyl-tRNA to introduce variations of amino acids
| Project/Area Number |
16K05836
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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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| Research Field |
Bio-related chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Fujino Tomoko 東京大学, 物性研究所, 助教 (70463768)
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| Project Period (FY) |
2016-04-01 – 2021-03-31
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| Keywords | トリアゾール / RNA / クリック化学 / mRNA / duplex |
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| Outline of Final Research Achievements |
We developed a high-efficient synthesis method of triazole-linked nucleic acid using click chemistry for nucleic acid elongation reaction and realized its functional development in life science. In searching for a click-linking method between RNA and amino acid planned at the beginning, azidation to the DNA end and the click-linking method were developed. These methods enabled us to realize a convenient double-stranded DNA template preparation for next-generation DNA sequencers. In addition, we switched the research target from modified tRNA to more challenging modified mRNA without any examples. We realized modified mRNA with a non-phosphate-linked codon for the first time. We also clarified the effect of the triazole linkages in the double-strand formation of such modified RNA from the thermodynamic analysis.
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| Free Research Field |
有機合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
非リン酸型核酸は高い化学的・熱力学的安定性に加え，多様な機能性が期待される次世代型バイオ材料であるが，その合成上の制約により機能展開に至った例はごく限られていた．本研究では，高効率なクリック化学に着目して，糖保存・非リン酸型RNAでの最長の例を実現し，その二重鎖形成における熱力学的特性を初めて明らかにした．さらにこうした非リン酸型の機能展開として，これまで例のない翻訳反応におけるmRNAとしての機能性評価や，次世代シークエンサーのための鋳型DNA調整法を実現した．本研究により，これまでほとんど明らかとなってきていない非リン酸型RNA・DNAの機能性開拓を達成した．
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