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2005 Fiscal Year Final Research Report Summary

Functionalization of oligonucleotides capable to form alternate-stranded triplex containing stereoisomeric nucleotide units

Research Project

Project/Area Number 15550144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionGunma University

Principal Investigator

SHINOZUKA Kazuo  GUNMA UNIVERSITY, Chemistry, Professor, 工学部, 教授 (20206105)

Co-Investigator(Kenkyū-buntansha) MORIGUCHI Tomohisa  GUNMA UNIVERSITY, Chemistry, Associate Professor, 工学部, 助教授 (70334133)
Project Period (FY) 2003 – 2005
Keywordsα-β chimeric oligoDNA / intercalator / alternate-stranded triplex / novel non-nucleosidic component / diastereomer / pyrimidine-gap / metal complex / functional chimera DNA
Research Abstract

A novel phosphoramidite derivative of a dinucleoside phosphotriester unit bearing an intercalative moiety at its internucleotide linkage in a stereospecific manner was prepared and successfully incorporated into the middle portion of α-β chimeric oligoDNA. One of the resulting stereoisomeric chimera DNAs strongly enhances the thermal stability of an alternate-stranded triplex formed between the chimera and a double-stranded DNA. On the other hand, the duplexes containing the oligomers bearing the same unit failed to show any Tm increment (stabilization) effect regardless of the stereochemistry of the phosphorous atom bearing the intercalative moiety. Thus, the stabilizing effect of the current dinucleoside unit seems to be specific to the DNA triplex.
An anthraquinone derivative conjugated with 2,2-bis(hydroxymethyl)propionic acid as a novel non-nucleosidic component was synthesized and successfully incorporated into an internal region of 14-mer triplex-forming oligonucleotide (TFO) via … More the phosphoramidite method. The resulted novel TFO exhibits remarkable enhancement effect on the thermal stability of a DNA triplex upon binding to a pyrimidine-gap containing polypurine sequence.
Novel α-β chimeric oligodeoxynucleotides bearing an intercalator-conjugated nucleobase located at the internal 4-nt linker region were synthesized, and their triplex-stabilizing property was examined. The triple helical DNA formed between the modified chimera DNA and double-stranded DNA exhibited remarkable thermal stability ; however, the position of the intercalator-conjugated nucleobase had little influence on the stability. Among the examined, modified chimera DNA bearing the two intercalator-conjugated nucleobases at adjacent positions exhibited the highest stability.
Novel diastereomeric α-β chimeric oligodeoxynucleotides bearing a propionic acid derivative of an anthraquinone-polyamine conjugate in the "linker" region were synthesized. Upon hybridization with double-stranded DNA, the modified chimera DNAs formed substantially stable alternate-stranded triplex even at near physiological pH. Furthermore, the triplex-stabilizing effect brought about by the incorporation of the derivative was almost regardless of the stereochemistry of the derivative.
Novel conjugate composed of an intercalator-metal ligand-2,2-bis(hydroxymethyl)propionic acid was prepared. The conjugate forms complexes with divalent metal ions such as Fe^<2+>, Cu^<2+>, Zn^<2+>, etc. Among them, the Fe^<2+> complex cleaves double-stranded DNA, efficiently. A study to utilize a functional chimera DNA bearing the complex as a sequence specific gene regulator is now under way. Less

  • Research Products

    (12 results)

All 2006 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Modified α-β chimeric oligoDNA bearing a multi-conjugate of 2, 2-bis (hydroxymethyl)propionic acid/anthraquinone/polyamine exhibited improved and stereo-nonspecific triplex-forming ability.2006

    • Author(s)
      A.T.M.Z.Azam, T.Moriguchi, K.Shinozuka
    • Journal Title

      Chemical Communications

      Pages: 335-337

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Modified α-β chimeric oligoDNA bearing a multi-conjugate of 2,2-bis(hydroxymethyl)propionic acid/anthraquinone/polyamine exhibited improved and stereononspecific triplex-forming ability.2006

    • Author(s)
      A.T.M.Z.Azam, T.Moriguchi, K.Shinozuka
    • Journal Title

      Chemical Communications

      Pages: 335-337

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis and alternate-stranded triple helix forming ability of novel anthraquinone modified α-β chimeric DNA2005

    • Author(s)
      T.Moriguchi, A.T.M.Z.Azam, K.Shinozuka
    • Journal Title

      Nucleic Acids Res. Sym. Ser., 49

      Pages: 7-8

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthesis and alternate-stranded triple helix forming ability of novel anthraquinone modified α-β chimeric DNA.2005

    • Author(s)
      T.Moriguchi, A.T.M.Z.Azam, K.Shinozuka
    • Journal Title

      Nucleic Acids Res.Sym.Ser. 49

      Pages: 7-8

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel anthraquinone conjugate of 2,2-bis(hydroxymethyl)propionic acid incorporated to a TFO with phosphotriester linkage facilitates triplex formation with dsDNA. bearing a Pyrimidine-gapped polypurine sequence.2004

    • Author(s)
      M.Sato, T.Moriguchi, K.Shinozuka
    • Journal Title

      Bioorganic and Medicinal Chemistry Letters 14

      Pages: 1305-1308

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] α-β chimeric oligoDNA bearing intercalator-conjugated nucleoside inside the linker sequence remarkably improves thermal stability of an alternate-stranded triple helix.2004

    • Author(s)
      A.T.M.Z.Azam, M.Hasegawa, T.Moriguchi, K.Shinozuka
    • Journal Title

      Bioorganic and Medicinal Chemistry Letters 14

      Pages: 5747-5750

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthesis and alternate-stranded triplex forming ability of novel α-β chimeric oligonucleotides bearing an intercalator-conjugated nucleobase.2004

    • Author(s)
      A.T.M.Z.Azam, M.Hasegawa, T.Moriguchi, K.Shinozuka
    • Journal Title

      Nucleic Acids Res. Sym. Ser., 48

      Pages: 207-208

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel anthraquinone conjugate of 2,2-bis(hydroxymethyl)propionic acid incorporated to a TFO with phosphotriester linkage facilitates triplex formation with dsDNA bearing a Pyrimidine-gapped polypurine sequence.2004

    • Author(s)
      M.Sato, T.Moriguchi, K.Shinozuka
    • Journal Title

      Bioorganic and Medicinal Chemistry Letters 14

      Pages: 1305-1308

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] α-β chimeric oligcDNA bearing intercalator-conjugated nucleoside inside the linker sequence remarkably inproves thermal stability of an alternate-stranded triple helix.2004

    • Author(s)
      A.T.M.Z.Azam, M.Hasegawa, T.Moriguchi, K.Shinozuka
    • Journal Title

      Bioorganic and Medicinal Chemistry Letters 14

      Pages: 5747-5750

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis and alternate-stranded triplex forming ability of novel α-β chimeric oligonucleotides bearing an intercalator-conjugated nucleobase.2004

    • Author(s)
      A.T.M.Z.Azam, M.Hasegawa, T.Moriguchi, K.Shinozuka
    • Journal Title

      Nucleic Acids Res.Sym.Ser. 48

      Pages: 207-208

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel dinucleoside phosphotriester unit conjugated with an intercalator moiety in a Stereospecific manner enhances thermal stability of an alternate-stranded triple helix.2003

    • Author(s)
      T.Miyashita, N.Matsumoto, T.Moriguchi, K..Shinozuka
    • Journal Title

      Tetrahedron Letters 44

      Pages: 7399-7402

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Novel dinucleoside phosphotriester unit conjugated with an intercalator moiety in a Stereospecific manner enhances thermal stability of an alternate-stranded triple helix.2003

    • Author(s)
      T.Miyashita, N.Matsumoto, T.Moriguchi, K.Shinozuka
    • Journal Title

      Tetrahedron Letters 44

      Pages: 7399-7402

    • 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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