| Project/Area Number |
13132203
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | The University of Tokyo |
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Principal Investigator |
WADA Takeshi The University of Tokyo, Graduate School of Frontier Sciences, Associate Professor, 大学院新領域創成科学研究科, 助教授 (90240548)
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| Project Period (FY) |
2001 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥37,000,000 (Direct Cost: ¥37,000,000)
Fiscal Year 2004: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 2003: ¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 2002: ¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2001: ¥9,800,000 (Direct Cost: ¥9,800,000)
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| Keywords | Boranophosphate DNA / Phosphorothioate DAN / Antisense DNA / Artificial nucleic acids / Stereocontrolled synthesis / Oligonucleotide synthesis / Solid-phase synthesis / Oligonucleotide therapeutics / ホスホロチオエートRNA / RNAi / 立体選択的合成 / オキサザホスホリジシ法 / ホスホロアミダイト法 / ホスホロシオエートDNA / オキサザホスホリジン法 / ジアステレオ選択的合成 / 無保護H-ホスホネート法 / N-アシル化DNA / 光クロスリンク核酸 / 2-アジドデオキシアデノシン / DNA / DNA相互作用 / RNA相互作用 / タンパク質相互作用 |
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| Research Abstract |
New methods for the highly efficient synthesis of artificial nucleic acids, which are useful as drugs or functional materials, were developed. Boranophosphate DNAs are regarded as potentially useful antisense molecules or stable nucleic acid-based functional materials. We developed a new method for the synthesis of the boranophosphate DNAs on the basis of a new boranophosphorylation reaction (boranophosphotriester approach). We also developed a new reaction for the transformation of the boranophosphate DNAs into the corresponding H-phosphonate DNAs, which are useful intermediates for the synthesis of a wide variety of backbone-modified DNA analogs. Among these DNA analogs, phosphorothioate DNAs are most widely used for antisense drugs to date. However, the currently used phosphorothioate DNAs are random mixtures of diastereomers owing to the phosphorous chirality. We developed a new method for the stereocontrolled synthesis of phosphorothioate DNAs by the use of nucleoside 3'-oxazaphospholidine derivatives as monomers (oxazaphospholidine approach). The method was successfully applied to the stereocontrolled synthesis of phosphorothioate RNAs as well as other backbone-modified nucleic acid analogs.
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