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2003 Fiscal Year Final Research Report Summary

Synthesis and properties of novel artificial nucleic acid analogs having chiral backbones

Research Project

Project/Area Number 14580607
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bioorganic chemistry
Research InstitutionThe University of Tokyo

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)

Project Period (FY) 2002 – 2003
Keywordsnucleic acid analog / artificial nucleic acid / polyester / solid-phase synthesis / L-serine / peptide nucleic acid / PNA / condensing reagent
Research Abstract

Peptide nucleic acid(PNA), an oligonucleotide mimic, has an achiral polyamide backbone, to which nucleobases are attached. Since PNA binds to single stranded DNA and RNA as well as to double stranded DNA, it is regarded as a potentially useful molecule for antisense strategy. It is well known that the PNA-DNA and PNA-RNA duplexes are more stable than the corresponding DNA-DNA and DNA-RNA duplexes. However, the recent structural studies on PNA-DNA and PNA-RNA duplexes by NMR indicated that the conformation of PNA in such complexes was not optimal RNA because the helical pitch of PNA is much larger than that of DNA and RNA. In this study, I tried to synthesize a new type of DNA analog derived from L-serine with ester linkages, serine-based nucleobase-linked polyester (SNE). The present DNA analog bearing a polyester backbone is expected to have a shorter helical pitch compared with that of PNA, which is identical for the hybridization with complementary nucleic acids. I developed a new strategy for the synthesis of a polyester-type nucleic acid analog consist of N-(thymin-1-yl)acetyl L-serine. The monomer unit bearing thymine base was synthesized from L-serine ethyl ester by a three-step reaction in good yield without racemization. 3-Nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1-yl)phosphonium hexafluorophosphate (PyNTP) was found to be highly effective for the rapid ester bond formation without racemization. 2-Phenyl-2-(trimethylsilyl)ethyl group was successfully employed as a carboxyl protecting group in solution-phase synthesis. Solid-phase synthesis of SNE was achieved by using a novel type of linker and amino-protecting groups that can be removed under mild neutral conditions.

  • Research Products

    (15 results)

All 2003 2002

All Journal Article (15 results)

  • [Journal Article] Solid-phase Synthesis of a Novel Polyester analog of Nucleic Acid Bearing Serine Backbone2003

    • Author(s)
      Wada, T., Murata, A., Tsuneyama, T., Saigo, K.
    • Journal Title

      Peptide Science 40

      Pages: 159-160

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthesis of Chiral Oligopeptides which Recognize Double-stranded DNAs2003

    • Author(s)
      Wada, T., Funayama, S., Shoji, Y., Saigo, K.
    • Journal Title

      Peptids Science 40

      Pages: 181-182

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An Oxazaphospholidine Approach for the Stereocontrolled Synthesis of Ologonucleoside Phosphorothioates2003

    • Author(s)
      Oka, N., Wada, T., Saigo, K.
    • Journal Title

      J. Am. Chem. Soc. 125

      Pages: 8307-8317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Diastereocontrolled Synthesis of Phosphorothioate DNA via an Oxazaphospholidine Approach Using a Novel Class of Activators, Dialkyl(cyanomethyl)-ammonium salts2003

    • Author(s)
      Oka, N, Wada, T., Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1411-1413

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthesis of Dinucleoside Boranophosphates by a Boranophosphotriester2003

    • Author(s)
      Wada, T., Shimizu, M., Oka, N., Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1471-1473

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Reaction Mechanism for the Sterercontrolled Synthesis of Phosphorothioate DNA by the Oxazaphospholidine Approach2003

    • Author(s)
      Wada, T., Oka, N, Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1431-1433

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Solid-phase Synthesis of a Novel Polyester Analog of Nucleic Acid Bearing Serine Backbone2003

    • Author(s)
      Wada, T., Murata, A., Tsuneyama, T., Saigo, K.
    • Journal Title

      Peptide Science 40

      Pages: 159-150

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis of Chiral Oligopeptides which Recognize Double-stranded DNAs2003

    • Author(s)
      Wada.T., Funayama, S., Shoji, Y., Saigo, K.
    • Journal Title

      Peptide Science 40

      Pages: 181-182

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An Oxazaphospholidine Approach for the Stereocontrolled Synthesis of Oligonucleoside Phosphorothioates2003

    • Author(s)
      Oka, N, Wada.T., Saigo, K.
    • Journal Title

      J.Am.Chem.Soc. 125

      Pages: 8307-8317

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Diastereocontrolled Synthesis of Phosphorothioate DNA via an Oxazaphospholidine Approach Using a Novel Class of Activators, Dialkyl(cyanomethyl)ammonium salts2003

    • Author(s)
      Oka, N, Wada, T., Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1141-1143

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Reaction Mechanism for the Sterercontrolled Synthesis of Phosphorothioate DNA by the Oxazaphospholidine Approach2003

    • Author(s)
      Wada.T., Oka, N, Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1471-1473

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis of Dinucleoside Boranophosphates by a Boranophosphotriester Approach2003

    • Author(s)
      Wada.T., Shimizu, M., Oka, N., Saigo, K.
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids 22

      Pages: 1431-1433

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Diastereocontrolled Synthesis of Dinucleoside Phosphorothioates Using a Novel Activators, Dialkyl(cyanomethyl)ammonium Tetrafluoroborates2002

    • Author(s)
      Oka, N, Wada.T., Saigo, K.
    • Journal Title

      J.Am.Chem.Soc. 124

      Pages: 1962-1963

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A New Boranophosphorylation Reaction for the Synthesis of Deoxyribonucleoside Boranophosphates2002

    • Author(s)
      Wada.T., Shimizu, M., Oka, N., Saigo, K.
    • Journal Title

      Tetrahedron Lett. 43

      Pages: 4137-4140

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Taurine as a Constituent of Mitochondrial tRNAs : New Insight into the Functions of Taurine and Human Mitochondrial Diseases2002

    • Author(s)
      Suzuki, T., Suzuki, T., Wada.T., Saigo, K., Watanabe, K.
    • Journal Title

      EMBO J. 21

      Pages: 6581-6589

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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