| Project/Area Number |
09304061
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Inorganic chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGANO Tetsuo INSTI, DEPARTMENT, TITLE OF POSITION GRAD SCHOOL PHAR SCI, THE UNIVERSITY OF TOKYO, PROFESSOR, 大学院・薬学系研究科, 教授 (20111552)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Tsunehiko GRAD SCHOOL PHAR SCI, THE UNIVERSITY OF TOKYO, ASSO. PROF., 大学院・薬学系研究科, 助教授 (50173159)
MASHINO Tadahiko KYORITSU PHAR COL, ASSO. PROF., 助教授 (90165697)
OHTA Shigeru SCHOOL MED, HIROSHIMA UNIV, PROFESSOR, 医学部・総合薬学科, 教授 (60160503)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 1999: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1998: ¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1997: ¥17,000,000 (Direct Cost: ¥17,000,000)
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| Keywords | superoxide / nitric oxide / zinc / fluorescent probe / reactive oxygen species / bioimaging / nitric oxide synthase / superoxide dismutase / 光線力学療法 |
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| Research Abstract |
(1) DEVELOPMENT OF VONEL ZINC FLUORESCENT PROBES EXCITTABLE WITH VISIBLE LIGHT FOR BIOLOGICAL APPLICATIONS
We have developed novel Zn2+ fluorescent probes that are excited by visible light. The probes can selectively detect Zn2+ at physiological pH. The compounds are expected to offer a useful tool for measuring Zn2+ concentration in living cells. Fluorescent probes for Zn2+ have previously been developed. But they are unsuitable for measuring Zn2+ concentration in biological samples in vivo because they either must be excited at ultraviolet wavelengths (which can damage cells) or they operate at a physiologically incompatible alkaline pH. To fashion the new probes we designed and synthesized the fluorophore 6-hydroxy-9-[4-(4, 7, 10-trimethyl-1, 4, 7, 10-tetraazacyclododecan-1-yl)] phenyl-3-one, coupling directly to a macrocyclic ployamine. In various experiments we showed that the fluorescence intensity of both probes increased dramatically as the concentration of Zn2+ is raised. Fluorescence is not affected by high concentrations of Na+, K+, or Mg2+, suggesting that the probes are specific for Zn2+.
(2) DEVELOOPMENT OF NOVEL NIRIC OXIDEFLUORESCENT PROBES
We have highly selective nitric oxide fluorescent probes, which is practically useful for bioimaging.
(3) DEVELOPMENT OF NOVEL Fe COMPLEXES WITH SUPEROXIDE DISMUTASE ACTIVITY AND THEIR APPLICATION
To investigate the relationship between the two structures of Fe-TPEN and superoxide dismutase (SOD), we synthesized novel Fe(II) complexes of TPEN analogues and measures their SOD activity by the cyt. c method. The results show that the substitution reaction of a ligand with superoxide or the coordination of superoxide is essential for Fe(II)TPEN analogue complexes to have SOD activity.
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