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The Development of the Novel Reactive Nucleobases to the Duplex DNA

Research Project

Project/Area Number 13680673
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionKyushu University

Principal Investigator

NAGATSUGI Fumi  Faculty of Pharmaceutical Sciences, Assistant Prof., 薬学研究院, 助手 (90208025)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords2-amino-6-vinilpurine / antisense / reactive nucleic acids / genome targeted chemistry / point mutation by chemical method / クロスリンク反応 / 3本鎖形成 / 反応性オリゴマーDNA / 2-アミノ-6-ビニルプリン / 点変異誘起
Research Abstract

The selective reaction to the gene would have the potential for site-directed mutation. In 2001, we have demonstrated that TFO bearing 2-amino-6-vinypurine derivative achieves triplex mediated cross-linking with high selectivity toward the cytosine of the G-C or the adenosine of the T-A target site. In 2002, we have investigated the use of this reactive TFO to target mutations to a target site in a shuttle vector plasmid, which replicates in mammalian cells. TFOs bearing of this reactive molecular produced adducts only at the complementary position of this reactive molecular and thereby introduced mutations at that site during replication/repair of the plasmid in mammalian cells. In the addition, we attempted the improvement of the reactivity by some modification of this molecule. But this experiment was not successful, because the oligonucleotides bearing modified molecule were not able to form the stable triple helix. It was clear that the triple helix formation was effected by a small change of structure. Now we investigate to develop of the new molecular by using the post modification method and we expect that we can get a new molecule with effective reactivity to gene.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] F.Nagatsugi, D.Usui, T.Kawasaki, M.Maeda, S.Sasaki: "Selective Reaction to a Flipping Cytidine of the Duplex DNA Mediated by Triple Helix Formation"Bioorg & Med.Chem Lett.. 11(9). 343-345 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi, F., Tokuda, N., Maeda, M., Sasaki, S: "A New Reactive Nucleoside Analogue for Highly Reactive and Selective Cross-Linking Reaction to Cytidine under Neutral Condition"Bioorg & Med.Chem Lett.. 11(9). 2577-2579 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi, F., Tokuda, N., Kawasaki, T., Maeda, M., Sasaki, S: "Efficient Cross-Linking to Cytidine under Neutral Conditions Using the 2-Amino-6-Vinylpurine Derivatives Having an Additional Activating Group"Nucleic Acids Res.Suppl. 44. 87-88 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki, S., Yamauchi, H., Nagatsugi.F., Takahashi, R., Taniguchi, Y., Maeda, M.: "W-Shape Nucleic Acid (WNA) for Selective Formation of Non-Natural Anti-Parallel Triplex Including a TA Interrupting Site"Tetrahedron Letters. 42(39). 6915-6918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] F.Nagatsugi, T.Kawasaki, N.Tokuda, M.Maeda, S.Sasaki: "Site-Directed Alkylation to cytidine within Duplex by the Oligonucleotides Containing Functional Nucleobases"Nucleoside, Nucleotides & Nucleic Acids,. 20. 915-918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi, F., Matsuyama, Y., Maeda, M., Sasaki, S.: "Selective cross-linking to the adenine of the TA interrupting site within the triple helix"Bioorg Med Chem Lett. 12. 487-489 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi F., Sasaki S., Miller P.S., Seidman M.M.: "Mutagenesis Targeted by Triple-Helix Forming Oligonucleotides Containing A Reactive Nucleoside Analogue"Nucleic Acids Res.Suppl.. 2. 35-36 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Md.Monsur Ali, Nagatsugi F., Yamamoto F., Maeda M., Sasaki S: "2-Amino-6-Vinylpurine as a Tool of Post Synthetic Conjugation of Oligonucleotides with Radio-, Spin-, Fluorescence Label and Peptides"Nucleic Acids Res.Suppl.. 2. 149-150 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi F., Sasaki S., Miller P.S., Seidman M.M.: "Site-Specific Mutagenesis by Triple-Helix Forming Oligonucleotides Containing a Reactive Nucleoside Analogue"Nucleic Acids Research. 6. e31-e41 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] F. Nagatsugi, D. Usui, T. Kawasaki, M. Maeda, S. Sasaki: "Selective Reaction to a Flipping Cytidine of the Duplex DNA Mediated by Triple Helix Formation"Bioorg. Med. Chem. Lett.. 11. 343-345 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumi Nagatsugi, Natsuko Tokuda, Minoru Maeda and Shigeki Sasaki: "A new reactive nucleoside analogue for highly reactive and selective cross-linking reaction to cytidine under neutral conditions"Bioorg. Med. Chem. Lett.. 11. 2577-2579 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shigeki Sasaki, Hiroyuki Yamauchi, Fumi Nagatsugi, Ryo Takahashi, Yosuke Taniguchi and Minoru Maeda: "W-shape nucleic acid (WNA) for selective formation of non-natural anti-parallel triplex including a TA interrupting site"Tetrahedron Lett.. 42(39). 6915-6918 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] F. Nagatsugi, T. Kawasaki, N. Tokuda, M. Maeda, S. Sasaki: "Site-Directed Alkylation to cytidine within Duplex by the Oligonucleotides Containing Functional Nucleobases"Nucleoside, Nucleotides & Nucleic Acids. 20. 915-919 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumi Nagatsugi, Natsuko Tokuda, Minoru Maeda and Shigeki Sasaki: "Efficient cross-linking to cytidine under neutral conditions using the 2-amino-6-vinylpurine derivative having an additional activating group"Nucleic Acids Res. Supplement. 1. 87-88 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi F, Matsuyama Y, Maeda M, Sasaki S: "Selective cross-linking to the adenine of the TA interrupting site within the triple helix"Bioorg Med Chem Lett.. 12. 487-489 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi F., Sasaki S., Miller P. S. and Seidman M. M.: "A new reactive nucleoside analogue for highly reactive and selective cross-linking reaction to cytidine under neutral conditions"Nucleic Acids Res. Suppl.. 2. 35-36 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Md. Monsur Ali, Nagatsugi F., Yamamoto F., Maeda M., Sasaki S.: "2-Amino-6-Vinylpurine as a Tool of Post Synthetic Conjugation of Oligonucleotides with Radio-, Spin-, Eluorescence Label and Peptides"Nucleic Acids Res. Supp.. 2. 149-150 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagatsugi F, Sasaki S, Miller P. S, and Seidman M. M.: "Site-Specific Mutagenesis by Triple-Helix Forming Oligonucleotides Containing a Reactive Nucleoside Analogue."Nucleic Acids Research. 6. e31-e40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fumi Nagatsugi et al.: "Selective cross-linking to the adenine of the TA interrupting site within the triple helix"Bioorg Med Chem Lett. 12. 487-489 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fumi Nagatsugi et al.: "A new reactive nucleoside analogue for highly reactive and selective cross-linking reaction to cytidine under neutral conditions"Nucleic Acids Res. Suppl.. 2. 35-36 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fumi Nagatsugi et al.: "2-Amino-6-Vinylpurine as a Tool of Post Synthetic Conjugation of Oligonucleotides with Radio-, Spin-, Fluorescence Label and Peptides"Nucleic Acids Res Supp. 2. 149-150 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fumi Nagatsugi et al.: "Site-Specific Mutagenesis by Triple-Helix Forming Oligonucleotides Containing a Reactive Nucleoside Analogue"Nucleic Acids Res. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagatsugi, F., Tokuda, N., Maeda, M., Sasaki, S: "A New Reactive Nucleoside Analogue for Highly Reactive and Selective Cross-Linking Reaction to Cytidine under Neutral Condition"Bioorg & Med. Chem Lett.. 11(9). 2577-2579 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagatsugi, F., Matsuyama, Y., Maeda, M., Sasaki, S.: "Selective Cross-linking to the Adenine of the TA Interrupting Site within Homopurin Homopyrimidine Duplex"Bioorg & Med. Chem Lett.. 12(3). 487-489 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagatsugi, F., Tokuda, N., Kawasaki, T., Maeda, M., Sasaki, S.: "Efficient Cross-Linking to Cytidine under Neutral Conditions Using the 2-Amino-6-Vinylpurine Derivatives Having an Additional Activating Group"Nucleic Acids, Symp. Ser.. 44. 87-88 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sasaki, S., Yamauchi, H., Nagatsugi, F., Takahashi, R., Taniguchi, Y., Maeda, M.: "W-Shape Nucleic Acid (WNA) for Selective Formation of Non-Natural Anti-Parallel Triplex Including a TA Interrupting Site"Tetrahedron Letters. 42(39). 6915-6918 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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