| Project/Area Number |
04453031
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
天然物有機化学
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| Research Institution | TOKYO INSTITUTE OF TECHNOLOGY |
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Principal Investigator |
SEKINE Mitsuo TOKYO INSTITUTE OF TECHNOLOGY, FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, ASSOCIATE PROFESSOR, 生命理工学部, 助教授 (40111679)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Takeshi TOKYO INSTITUTE OF TECHNOLOGY, FACULTY OF BIOSCIENCE AND BIOTECHNOLOGY, RESEARCH, 生命理工学部, 助手 (90240548)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1993: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | ANTISENCE NUCLEIC ACID / 2'-PHOSPHATE / RNA / CHEMICALSYNTHESIS / HIV / SOLID PHASE SYNTHESIS / ENZYME RESISTANCE / AMIDITE / アンチセンス核酸 / 酸素耐性 / 2'-リン酸化RNA / アミダイト試薬 / エイズ / 環状シリルエーテル / 保護基 / 2'、3'-リン酸基転移 / チオリン酸基 |
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| Research Abstract |
This year, we have tried to study the development of new organic reactions required for the synthesis of 2'-phosphorylated RNAs. As the result, we have achieved the following results : First, we found that bis(2-cyano-1, 1-diamethylethyl)phosphoryl can be used not only as a 2'-hydroxyl protecting groups but also as a precursor of the 2'-phosphate group. This protected phosphoryl group was found to be quite stable upon removal of a 3', 5-cyclic silyl protecting group with HF/Py in dichloromethane and not to migrate from the 3'-2' hydroxyl functions. This finding led us to realize the construction of key intermediates, 2'-phosphorylated 3'-phosphoramide units which were required throughout this study. The builiding units were utilized for the solid phase synthesis of 2'-phosohorylated yridylate derivatives. We could synthesize 2, 4, 6, and 10mers of 2'-phosphorylated uridylated uridylates in good yields. They were found to be resistant to acid and alkaline conditions as well as enzymatic digestion with spleen phosphodiesterase. In particular, the 10 mer proved to have an unique structure as evidenced by NMR.At the present time, we are studying the binding ability of these new nucleic acid derivatives for target DNA or RNA fragments.
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