| Project/Area Number |
59470118
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Faculty of Pharmaceutical Sciences, University of Tokyo |
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Principal Investigator |
HIROBE Masaaki Faculty of Pharmaceutical Sciences, University of Tokyo Professor, 薬学部, 教授 (20012594)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Tsunehiko Faculty of Pharmaceutical Sciences, University of Tokyo Research Associate, 薬学部, 助手 (50173159)
MASHINO Tadahiko Faculty of Pharmaceutical Sciences, University of Tokyo Research Associate, 薬学部, 助手 (90165697)
OHTA Shigeru Faculty of Pharmaceutical Sciences, University of Tokyo Research Associate, 薬学部, 助手 (60160503)
NAGANO Tetsuo Faculty of Pharmaceutical Sciences, University of Tokyo Associate Professor, 薬学部, 助教授 (20111552)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1986: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1984: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Cytochrome P450 / FeTPPCl / Electron Transfer / Effector / Oxygenase / Biomimetic Reaction / Flavin |
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| Research Abstract |
Cytochrome P450 and its electron transfer system play an important role in metabolizing biomolecules and xenobiotics. The P450 enzyme catalyzes the oxidation of various substrates by the introduction of one oxygen atom into a substrate from dioxygen. Our research projects concerning the oxidation system are shown below.
(1) Much interests have been focused on the mechanism of the electron transfer between the flavin and the heme. Hence, intramolecular linked flavin- porphyrin complexes have been prepared to elucidate the flavin-heme electron transfer and its transient nature. Furthermore, N-benzyl-1,4- dihydronicotinamide compounds have been synthesized as the model of NAD(P)H coenzyme. Then, the steric and electronic effects have been discussed based on UV spectra and redox potential data.
(2) P450 enzyme model systems have been studied to reveal the enzyme mechanism of P450. Furthermore, polypeptide-bound Fe(III)TPPCl has been prepared to consider environmental effects of protein around hemin in P450.
(3) In cytochrome P450 monooxygenations, metalloporphyrin oxenoid complex is considered to be an ultimate reactive species which is responsible for the oxidation of substrates. In the research, the formation mechanism of the metalloporphyrin oxenoid via acylperoxy metalloporphyrin was proposed.
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