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Chemical Studies on Oxidative Damage and Reductive Repair of Nucleic Acids and Related Compounds

Research Project

Project/Area Number 62470136
Research Category

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

Allocation TypeSingle-year Grants
Research Field Chemical pharmacy
Research InstitutionKyoto University

Principal Investigator

YONEDA Fumio  Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 教授 (80040327)

Co-Investigator(Kenkyū-buntansha) TANAKA Kiyoshi  Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 助手 (50093266)
HARAYAMA Takashi  Faculty of Pharmaceutical Sciences, Kyoto University, 薬学部, 助手 (30025712)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsNucleic acid / Oxidative damage / Reductive repair / Thymidine epoxide / Thymidine bromohydrin / Radical mechanism / Adenine-1-oxide / グルタチオン / チミジンブロムヒドリン / トリアルキルフォスファイト還元 / 太陽光 / アデニン-1-オキシド / 核酸の破損 / チミジン / チミジンエポキシド / 核酸の修復 / クロスカップリング反応
Research Abstract

Nucleic acids (DNA,RNA) play important roles in transmission of essential genetic imformation in living cell. The oxidation of nucleic acids and related compoiunds by reactive oxygen species, such as hydrogen peroxide, hydroxy radical, superoxide anion, singlet oxygen, have recently been receiving much attention as they may be involved in mutagenesis, carcinogenesis and aging. On the other hand, protection against the damage and repairing of the damaged nucleic acids are seemed to be one of the vital inherent functions. We focused on oxidative damage and reductive repair of nucleic acids and related compounds from a chemical point of view and found following seceral remarkable results and some imformation.
1. Oxidation of pyrimidine bases, especially thymidine derivatives were investigated and structures of oxidation products were elucidated. Thus, thymidine derivatives were transformed into the epoxide with mcpba and into ring contracted imidazolone derivatives with superoxide ion. A p … More lausible mechanism was also presented. 2. Reaction of 1,3-dimethylthymine or thymidine epoxide with seceral amines and L-amino acid derivatives as a model reaction for nucleic acid-protein cross links was studied and the stereo-structures of the products were elucidated on the bases of chemical isomerization reaction, X-ray analysis and the specific rotation. 3. The bromhydrins, which were oxidatively damaged products of thymidine derivatives, were repaired with sunlight or heat via radical mechanism to regenerate the parent thymidine derivatives. A novel one-electron transfer system consisting of 1,5-dihydro-5-deazaflavin and flavin could be applicable to this reparing system under milder conditions. Furthermore, the bromohydrins were effectively reduced with a system of Cu(II)-ascorbic acid or with using coenzyme models, 1,5-dihydro-5-deazaflavin, 1,4-dihydroquinoline, in the presence of acid additive. 4. The diol of the thymidine derivatives, another type of oxidatively damaged product, was effectively converted to reduced original product with the phosphite reagent. 5. The adenine-1-oxide derivatives, the other oxidatively damaged components of nucleic acid, were reductively repaired by reduced form glutathione under irradiation with sunlight to give the corresponding adenine derivatives. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] 原山尚,米田文郎 他: Biochemical and Biophysical Research Communications. 148ー3. 995-1000 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 原山尚,米田文郎 他: Journal of The Chemical Society,Chemical Communications. 17. 1171-1172 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 原山尚,米田文郎 他: Journal of The Chemical Society,Perkin Trans.I. 9. 2555-2562 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 原山尚,米田文郎 他: Journal of The Chemical Society,Chemical Communications. 4. 238-239 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 田中圭,米田文郎 他: Journal of Heterocyclic Chemistry. 26. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 原山尚,田中圭,米田文郎 他: Journal of The Chemical Sciety,Chemical Communications. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Harayama; F. Yoneda et. al,: "On the Repair of Thymidine Bromohydrins, Damaged Nucleosides: A Possible New Model for the Damage and Reapir of Nucleic Acids" Biochemical and Biophysical Research Communications. 148-3. 995-1000 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Harayama; F. Yoneda et. al,: "Oxidation of Thymine Derivatives with Superoxide Ion" Journal of The Chemical Society, Chemical Communications. - - 17. 1171-1172 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Harayama; F. Yoneda et. al,: "Stereo-structures of Reaction Products of Thymidine Epoxides with Amines and L-Amino Acid Ethyl Esters" Journal of The Chemical Society, Perkin Trans. I. - - 9. 2555-2562 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Harayama; F. Yoneda et. al,: "The Repair of Thymine and Thymidine Bromohydrins, Models of Damaged Nucleic Acids, by a Copper(II) and Ascorbic Acid System" Journal of The Chemical Society, Chemical Communications. - - 4. 238-239 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] T. Harayama; K. Tanaka; F. Yoneda et. al,: "A Model One-electron Reduction System Consisting of 1,5-Dihydro-5-deazaflavin and Flavinium. Application to the Reductive Repair of 1,3-Dimethylthymine Bromohydrin as a Model of Damaged Nucleic Acid" Journal of The Chemical Society, Chemical Communications. - - -. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 原山尚,米田文郎 他: Nucleic Acids Research symposium Series. 19. 107-110 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 原山尚,米田文郎 他: Journal of The Chemical Society,Chemical Communications. 4. 238-239 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 米田文郎 他: Journal of Heterocyclic Chemistry. 26. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 原山尚,米田文郎 他: Jonrnal of The Chemical Society,Chemical Communications. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] TAKASHI HARAYAMA他: Biochem Biophs.Res.Commun.,. 148. 995-1000 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] TAKASHI HARAYAMA他: Nucleic Acids Symposium Series. 19. 107-110 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] TAKASHI HARAYAMA他: J.Chem.Soc.,Perkin Trans.1. (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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