| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Research Abstract |
DNA cleaving reagent is an essentical tool for the treatment of cancers and hereditary diseases. It is expected that the reagents that can cleavage specific sequence and specific structure of DNA selectively can be applied to the antitumor drugs and the artificial restriction enzymes.
In my approach to develope novel optical active dinuclear iron complexes that are capable of cleaving double-strand DNA simultaneously and sequence-selectively, I prepared six dinuclear ligands, (1,8-(N-anthranylmethyl)-bis(N',N'-dipyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (R or S-ABDC), 1,3-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (m-R-BDC or m-S-BDC), and 1,4-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (p-R-DBC or p-S-BDC).
Moreover, I investigated plasmid pUC 19 DNA cleaving activity by iron complexes, which are prepared by mixing of ligand with FeSO_4 in buffered solution in the presence of sodium ascorbate. All the iron complexes cleaved pUC 19 DNA efficiently and were found to cleave 281 base-pair DNA with a little selectivity, indicating that the dinuclear metal-chelating moiety that connected by the linker may be necessary for the sequence selectivity of DNA strand scission.
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