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Design and Synthesis of DNA-Cleaving Molecules

Research Project

Project/Area Number 02453023
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 有機化学一般
Research InstitutionKyoto University

Principal Investigator

SAITO Isao  Kyoto University, Faculty of Engineering, Professor, 工学部, 教授 (20026082)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Hiroshi  Kyoto Univ., Faculty of Engineering. Research Associate, 工学部, 助手 (50183843)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥4,400,000 (Direct Cost: ¥4,400,000)
KeywordsDNA Cleavage / Ene-diyne Antitumor Antibiotics / Artificial Restriction Enzym / Photo-DNA-Cleavage / Hydroxyl Radical Cenerator / 水酸ラジカル発生試薬 / 光DNA切断
Research Abstract

There has been great interest in designing reagents that bind to DNA duplex selectively at desired sequences. Such molecules equipped with a chemical or photochemical tag capable of modifying or cleaving DNA at the site of binding should have great prospects as "synthetic artificial restriction enzymes" and not least as gene-selective drugs. We have focused on the use of natural DNA-binders such as antitumor antibiotics, DNA-binding proteins or sequence-defined oligonucleotides in combination with photoactivated DNA-cleaving molecules. We have succeeded in designing a new sequence specific "photochemical DNA cleaver" that binds specifically to-5'-GG-3'sequence. This molecule named as "photo-Fenton-reagent" is widely used as a convenient source of hydroxyl radical. We also succeeded in designing a different type of DNA-cleaving molecules based on the conceit obtained from the work on the action mechanism of ene-diyne type antitumor antibiotics such as neocarzinostatin or esperamicin.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] 杉本 弘: "Specific Detection of Cー4' Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinostatin in DNA" J.Am.Chem.Soc.112. 5250-5257 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 永田 龍: "DNA Cleavage by Acyclic EneyneーAllene Systems related to Neocarzinostatin and EsperamicinーCalicheamicin" Tetrahedron Lett.31. 2907-2910 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 杉山 弘: "Highly Sequence Selective Photreaction of 5ーBromouracilーContaining deoxyhexanucleotide" J.Am.Chem.Soc.112. 6720-6721 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 杉山 弘: "BleomycinーMediated Degradation of AristeromycinーContaining DNA.Novel Dehydrogenation Activity of IronーBleomycin" J.Am.Chem.Soc.113. 2290-2295 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 松郷 誠一: "Bis(hydroperoxy)naphthaldiimide as a "PhotoーFenton Reagent";SequenceーSpecific Photocleavage of DNA" Angew.Chem.Int.Ed.Engl.30. 1351-1353 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 杉山 弘: "A Novel Cyclization Pathway in Activation of Necarzinostatin Chromophore by Thiol Under Physiological Conditions" Tetrahedron Lett.33. 515-518 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sugiyama: "Specific Detection of C4' Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinostatin in DNA" J. Am. Chem. Soc.,. 112. 5252-5257 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] R. Nagata: "DNA Cleavage by Acyclic Eneyne-Allene Systems related to Neocarzinostatin and Esperamicin-Calicheamicin" Tetrahedron Lett.31. 2907-2910 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] I. Saito: "Phthalimide Hydroperoxides as an Efficient Photochemical Hydroxyl Radical Generator" J. Am. Chem. Soc.112. 883-884 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sugiyama: "Highly Sequence Selective Photoreaction of 5-Bromouracil-Containing Deoxyhexanucleotide" J. Am. Chem. Soc.112. 6720-6721 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] I. Saito: "A New Method for the Synthesis of [3]-Cumulenes and Eneynecumulenes related to Neocarzinostatin Chromophore" Tetrahedron Lett.31. 7469-7472 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sugiyama: "Bleomycin-Mediated Degradation of Aristeromycin-Containing DNA. Novel Dehydrogenation Activity of Iron-Bleomycin" J. Am. Chem. Soc.113. 2290-2295 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] S. Matsugo: "Bis (hydroperoxy) naphthaldiimide as a "Photo-Fenton Reagent", Sequence Specific Cleavage of DNA" Angew. Chem. Int. Ed. Engl.30. 1351-1353 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] H. Sugiyama: "A Novel Cyclization Pathway in Activation of Neocarzinostain Chromophore by Thiol under Physiological conditions" Tetrahedron Lett.33. 515-518 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 杉山 弘: "Specific Detection of Cー4'Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinostatin in DNA" J.Am.Chem.Soc.112. 5252-5257 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 永田 龍: "DNA Cleavage by Acyclic EneyneーAllene Systems related to Neocarzinostatin and EsperamicinーCalicheamicin" Tetrahedeon Lett.31. 2907-2910 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 弘: "Highly Sequence Selective Photoreaction of 5ーBromouracilーContaining deoxyhexanucleotide" J.Am.Chem.Soc.112. 6720-6721 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 弘: "BleomycinーMediated Degradation of AristeromycinーContaining DNA.Novel Dehydrogenation Activity of IronーBleomycin" J.Am.Chem.Soc.113. 2290-2295 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松郷 誠一: "Bis(hydroperoxy)naphthaldiimide as a“PhotoーFenton Reagent";SequenceーSpecific Photocleavage of DNA" Angew.Chem.Int.Ed.Engl.30. 1351-1353 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 弘: "A Novel Cyclization Pathway in Activation of Neocarzinostatin Chromophore by Thiol Under Physiological Conditions" Tetrahedron Latt.33. 515-518 (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 杉山 弘: "Specific Detection of Cー4' Hydroxylated Abasic Sites Generated by Bleomycin and Neocarzinistatin in DNA" J.Am.Chem.Soc.112. 5252-5257 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 永田 龍: "DNA Cleavage by Acyclic EneyneーAllene Systems related to Neocarzinostatin and EsperamicinーCalicheamicin" Tetrahedron Lett.31. 2907-2910 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 斉藤 烈: "Phthalimide Hydroperoxide as an Efficient Photochemical Hydroxyl Radical Generator.A Novel DNAーCleaving Agent" J.Am.Chem.Soc.112. 883-884 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 杉山 弘: "Highly Sequence Selective Photoreaction of 5ーBromouracilーContaining Deoxyhexanucleotide" J.Am.Chem.Soc.112. 6720-6721 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 永田 龍: "IronーPeplomycin Catalyzed Oxygenation of Linoleic Acid" Tetrahedron Lett.31. 4485-4488 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 斉藤 烈: "A New Method for the Synthesis of [3]ーCumulenes and Eneynecumulenes Related to Neocarzinostatin Chromophore" Tetrahedron Lett.31. 7469-7472 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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