| Project/Area Number |
06453191
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | University of Tokyo |
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Principal Investigator |
NAGANO Tetsuo Univ. Tokyo, Fac. Pharm. Sci., Professor, 薬学部, 教授 (20111552)
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| Co-Investigator(Kenkyū-buntansha) |
MASHINO Tadahiko Kyoritsu College of Pharmacy, Associate Professor, 助教授 (90165697)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1994: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Superoxide / Superoxide Dismutase / Ion Complex / Spin Crossover Complex / Anti-inflammation / Paraquat / Anti-oxidant / 鉄-錯体 |
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| 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.
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