| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
To develop reagents for oxidative or hydrolytic cleavage of DNA, we have synthesized polynuclear metal complexes listed below and investigated their binding structure, the affinity to DNA, and the DNA cleaving reaction by using various spectroscopic measurements, X-ray crystallography, mass analysis, and agarose gel electrophoresis. Comparing the results with those of the corresponding mononuclear metal complexes, we have tried to analyze the factors that govern the specific orientation of the metal complexes and the reactivity.
(1)Histidine-containing peptide dinuclear copper(II) complexes.
(2)Hetero dinuclear copper(II) complexes with different coordination sites.
(3)Water-soluble salicylaldehyde Schiff base dinuclear Ni(II) complexes.
(4)Dinuclear copper(II) complex containing cis,cis-1,3,5-triaminocyclohexane (tach).
(5)Trinuclear zinc(II) complex of a 2,9-substituted phenanthroline derivative.
In the case of (1), it was shown that amino acid sequences of the peptides influence considerably the binding structure and cleavage. The crystal structure of the complex synthesized in (2) was determined and the presence of two different coordination sites was confirmed. The structure of the complex bound to DNA was investigated by DNA fiber ESR spectroscopy. Dinuclear Ni(II) Schiff base complexes (3) with tetraaminodiphenyl group (complex 1) and with aminoalcohol and pyrazole groups (complex 2) were synthesized and characterized. The oxidative DNA cleavage activity increased for complex 1 but decreased for complex 2, compared with those of the corresponding mononuclear complexes. In the case of (4), μ-η2:η2 peroxide complex was detected in the reaction of the complex with hydrogen peroxide, indicating that the hydroperoxo form was the active species for DNA cleaving reaction. Finally, a novel trinuclear Zn(II) complex (5) showed hydrolytic DNA cleaving reactivity much stronger than the corresponding mononuclear Zn(II) complex.
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