A study on the biosynthesis of guanosine monophosphate and the development of functional molecules targeting guanosine monophosphate synthetase
Project/Area Number |
17K05929
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Bio-related chemistry
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Research Institution | Gifu University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥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 / キサントシン / 7-デアザグアニン / グアノシン一リン酸 / キサントシン一リン酸 / GMP合成酵素 / AMP-XMP / グアノシン一リン酸合成酵素 / リン酸化 / 抗がん剤 |
Outline of Final Research Achievements |
Appropriately protected xanthosine derivatives were reacted with phosphoramidites activated by N-(cyanomethyl)dimethylammonium triflate (CMMT) developed by us. Subsequent oxidation/sulfurization and deprotection of the resultant phosphate esters afforded 2-O-phosphoryl/thiophosphorylxanthosine derivatives. The products were also fully deprotected by TBAF to afford xanthosine 2-phosphates. This new phosphorylation reaction should be useful for the development of molecular probes and therapeutic agents targeting the biosynthesis of guanosine monophosphate. Furthermore, a regioselective protection of 7-deazaguanine derivatives was achieved by using diphenylcarbamoyl chloride and DMAP. The appropriately protected 7-deazaguanine derivatives thus obtained were applied to the synthesis of 7-deazaguanosine derivatives which should be useful for the synthesis of 7-deazaxanthosine derivatives.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で開発した手法は、キサントシンの2位カルボニル基の初のリン酸化反応であり、グアノシン一リン酸の生合成中間体であるAMP-XMPの化学合成に欠かせない。また、本反応はAMP-XMPそのものだけでなく、その化学修飾アナログの合成にも応用できる。この様な化学修飾アナログは、グアノシン一リン酸の生合成経路を標的とする分子プローブや分子標的薬の合成への応用が期待される。以上のことから、本研究の成果は、これまで直接的な研究が難しかったグアノシン一リン酸の生合成中間体の性質や機能により詳細に迫るきっかけとなると同時に、この生合成経路を標的とする医薬品開発への道を拓くものであり、極めて意義深いと言える。
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Report
(4 results)
Research Products
(17 results)