Development of a method for the synthesis of biosynthetic intermediates of nucleic acids via phosphorylation of carbonyl group
| Project/Area Number |
26410175
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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 | Gifu University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 核酸の生合成 / カルボニル基のリン酸化 / ヌクレオチド / 酵素応答性分子 / イノシン / 蛍光標識化 / アデニロコハク酸 / リン酸 / 酵素反応中間体 / 蛍光プローブ / 抗がん剤 / チオリン酸 / 生合成 / グアニン一リン酸 / ホスホロアミダイト / 生合成中間体 / イノシン6-リン酸 |
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| Outline of Final Research Achievements |
This study aimed to develop a novel method for the synthesis of biosynthetic intermediates of nucleic acids and their chemically modified analogs. In order to achieve this goal, our original non-nucleophilic acidic activator, N-(cyanomethyl)dimethylammonium triflate (CMMT) was applied to the phosphitylation of carbonyl oxygen, finally enabling us to synthesize inosine 6-phosphate esters bearing various substituents, such as those for spin labeling and fluorescent labeling, on their phosphate groups. In addition, the stability of the inosine 6-phosphate esters toward cellular nucleases was examined to find that they were unstable and rapidly hydrolyzed in the presence of these enzymes. To solve this problem, we developed a method for the synthesis of inosine 6-thiophosphate esters, which were more stable toward these enzymes. The molecules developed in this study will be useful as molecular probes and therapeutic agents targeting the biosynthesis of nucleic acids.
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Report
(4 results)
Research Products
(34 results)
