| Project/Area Number |
09450337
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Synthetic chemistry
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| Research Institution | Gunma University |
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Principal Investigator |
SAWAI Hiroaki Gunma University, Department, Faculty of Engineering, Professor, 工学部, 教授 (70012648)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Hiroaki Gunma University, Department, Faculty of Engineering, Research Associate, 工学部, 助手 (90211820)
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| Project Period (FY) |
1997 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1997: ¥6,300,000 (Direct Cost: ¥6,300,000)
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| Keywords | DNA / Modified Nucleic Acids / 5-Substituted 2'-Deoxyuridines / 2'-Modiifed Nucleosides / 2-Substituted Deoxyuanosine Derivatives / RNA Cleaving Activity / Tris-Amine / Labeled DNA / トリスアシン / 2'-位置換スクレオシド / 2重鎖形成能 / 2'デオキシウリジン誘導体 / α-ヌクレオシド / アンチセンス核酸 / 標識化 |
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| Research Abstract |
We have developed facile synthesis of new 5-substituted thymidine derivatives, which are key compounds for the synthesis of modified DNAs. The modified oligodeoxyribonucleotides were prepared by a DNA synthesizer using the 5-substituted thymidine derivatives and the commercial available nucleoside phosphoramidites. The functional molecules were introduced into the modified oligonucleotides by pre- or post-synthetic modification methods. Post-synthetic modification is useful for the synthesis of various modified DNA in a final step of the DNA synthesis. Multi-functionalization of oligodeoxyribonucleotides could be accomplished by the new post-synthetic modification method. Various functional molecules such as a fluorescent agent, a chelating agent, a catalyst or an enzyme were incorporated into the modified oligodeoxyribonucleotides at the 5-position of the thymidine derivatives. The substituent groups on the modified oligodeoxyribonucleotides have positive or negative effect on the dup
… More
lex stability depending on the nature of the substituent group. Modified oligodeoxyribonucleotides bearing fluorescence were used for the studies of structure of DNA and of interaction of DNA and DNA binding protein. Complexes of a radioactive metal ion, Y-90 or In-111, with the modified oligodeoxyribonucleotides bearing a chelating agent whose sequence is complementary to N-Myc gene were used for fundamental studies of diagnosis and radiotherapy of some cancer related to the N-Myc. Other new modified oligonucleotides bearing α-nucleosides, 2-substituted deoxyguanosine, sugar-part 2'-modifed deoxyuridine or arabinosyl uridine were also prepared and their double-helix formation with the complementary DNAs and RNAs were studied. Tris (2-aminoethylamine), which was proved to be an acid-base catalyst for the cleavage of RNA in our previous study, was introduced into the modified oligodeoxyribonucleotides at 5-position of thymidine, 5-position of α-thymidine, 2-position of deoxyguanosine or 2'-position of uridine, and their RNA cleaving activities were assessed. The modified oligodeoxyribonucleotides bearing tris (2-aminoethylamine) at 2-modified deoxyguanosine showed strong sequence-specific RNA cleaving activity, if the bulge-out was created at the target site of RNA. Less
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