Project/Area Number |
17K19133
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Research Field |
Inorganic/Coordination chemistry, Analytical chemistry, and related fields
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Research Institution | Tohoku University |
Principal Investigator |
|
Research Collaborator |
SATO Yusuke
|
Project Period (FY) |
2017-06-30 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
Keywords | FIDアッセイ / 深赤色蛍光インジケーター / リボソームRNA A-site / A型インフルエンザウイルスRNA / ノンコーディングRNA / 蛍光インジケーター / 検出 |
Outline of Final Research Achievements |
We have successfully discovered that TO-PRO-3, a thiazole orange analogue with a trimethine bridge, functions as a deep-red fluorescenct indicator for the internal loop structure of the bacterial (Escherichia coli) ribosomal decoding region of the aminoacyl-tRNA site (A-site), which enables the assessment of A-site binding capability of various test compounds including blue and even-green-emitting compounds (Chem. Commun. 2019). TO-PRO-3 can also work as a useful indicator for the assessment of the binding capabilities of various test compounds for Influenza A virus RNA promoter region with a view toward the development of anti-influenza drug candidates (ChemBioChem. 2019). In addition, we have developed a new class of small heterocyclic ligands based on the 2-amino-5,6,7-trimethyl-1,8-naphthyridine structure for the bacterial A-site (Chem. Eur. J. 2018). Significantly, this ligand shows the tightest binding reported to date among non-aminoglycoside ligands.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、ポストゲノム時代における生命科学の飛躍的な発展を支える新しい解析技術(RNA結合リガンド)の創製を目指したものである。FID(Fluorescence indicator displacement assay)法に利用可能な深赤色蛍光インジケーター(λem > 650 nm)は世界的に報告例が無く、本研究が世界初の報告例となる。これにより、蛍光法の利点を最大限に活かしたスクリーニングが可能となるため、阻害剤開発の要となる技術基盤(スクリーニング法)を格段に発展させることが期待できる。なお、本研究成果の一部は、英国王立化学会速報誌(Chem. Commun.)の表紙にハイライトされた。
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