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1996 Fiscal Year Final Research Report Summary

Synthesis of Novel Iron Complexes with Superoxide Dismutase Activity

Research Project

Project/Area Number 06453191
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 医薬分子機能学
Research InstitutionUniversity of Tokyo

Principal Investigator

NAGANO Tetsuo  Univ. Tokyo, Fac. Pharm. Sci., Professor, 薬学部, 教授 (20111552)

Co-Investigator(Kenkyū-buntansha) MASHINO Tadahiko  Kyoritsu College of Pharmacy, Associate Professor, 助教授 (90165697)
Project Period (FY) 1994 – 1996
KeywordsSuperoxide / Superoxide Dismutase / Ion Complex / Spin Crossover Complex / Anti-inflammation / Paraquat / Anti-oxidant
Research Abstract

Recently it has been reported that superoxide (O_2) correlates with a cause of several diseases such as inflammation and carcinogenesis. Superoxide dismutase (SOD) serves a defensive role by catalyzing the conversion of O_2 to hydrogen peroxide and dioxygen. Therefore SOD and SOD mimics, which are complexes with SOD activity, are thought to be effective. We reported the first iron complexes, Fe (II)・TPEN (TPEN : N,N,N', N'-tetrakis (2-pyridylmethyl) ethylene diamine) Fe (III)・TPAA (TPAA : tris (N-(2-pyridylmethy)-2-amminoethyl)amine), which has high SOD activity not only in vitro but also in vivo. We also showed by X-ray structure analysis that Fe (II)・TPEN has two different structures, one of which is expressed as FeN6, the other as FeN5O.In order to clarify the relationship between these structures and SOD activity, we designed and synthesized TPEN analogues and investigated SOD activity, stability of oxygen and redox potentials of Fe (II) complexes of these chelators. The result suggested that,
1)it is necessary for SOD activity that complexes are labile and interact directly with O2-. Therefore FeN5O structrue of Fe (II)・TPEN is the important intermediate in the reaction with O2-.
2)the methyl group of the pyridine coordinated to Fe (II) has the influence on SOD activity and the stability to oxygen, but that of the uncoordinated pyridine has no effect on SOD activity.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Hidetoshi Yamashita: "Superoxid Dismutase in Developing Mouse Retina" Japanese Journal of Ophthalmology. 38. 148-161 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Eiji Hasegawa: "A Dual Effect of 1-Methyl-4-phenylpyridinium (MPP^+) Analogs on the Respiratory Chain of Bovine Heart Mitochondria" Arch.Biochem.Biophys. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dongchon Kang: "Changes of Energy Metabolism Induced by 1-Methyl-4-phenylpyridinium (MMP^+)-related Conpounds in PC12 cells" Arch.Biochem.Biophys. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 長野哲雄(分担執筆): "スーパーオキシドディスムターゼ発見物語" 東京化学同人, 70 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 長野哲雄(分担執筆): "SODと鉄錯体" 日本化学会, 244 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hidetoshi Yamashita: "Superoxide Dismutase in Developing Mouse Retina" Jpn J.Ophth.38. 148-161 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Eiji Hasegawa: "A Dual Effect of 1-Methyl-4-phenylpyridinium (MPP^+) Analogs on the Respiratory Chain of Bovine Heart Mitochondria" Arch. Biochem. Biophys.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dongchon Kang: "Changes of Energy Metabolism Induced by 1-Methyl-4-phenylpyridinium (MPP^+) Related Compounds in PC 12 Cells with Other Photosensitizer, Based on 1268 nm Emission" Arch. Biochem. Biophys.(in press).

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

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Published: 1999-03-09  

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