| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
The purpose of this research is to synthesize metalloporphyrins which can recognize a specific nucleotide sequence of nucleic acids and cleave them at a specific position, and to reveal the cleaving activity and interaction mechanism between them. First, I studied the interactions between nucleic acids and a water-soluble cationic porphyrin, tetramethylpyridylporphyrin (TMPyP). I employed synthetic DNA, RNA, and DNA RNA hybrids, and found that (1) TMPyP self-stacks in a minor groove of RNA duplexes, (2) TMPyP intercalates between the base-pairs of hybrid duplexes, and (3) TMPyP either binds to a minor groove electrostatically, or intercalates, depending on the sequence of DNA duplexes. I further studied the way to regulate the binding mode to DNA with the use of triplex formation. It was found that self-stacking and intercalation of the TMPyP were inhibited by the triplex formation, but the groove binding was promoted in that the number of binding sites of the TMPyP increased two-fold. The DNA cleaving activity of iron porphyrin and metal-free porphyrins was studied. The oxidative cleavage by peroxo-compounds was investigated in detail, and addition of imidazoles, which could be axial ligands of the iron, was found to promote the cleaving activity. A porphyrin periphery was introduced to give capability to recognize DNA sequences. In the porphyrin derivative having DNA-intercalating acridirie moiety, CD spectroscopy suggested that the porphyrin located in the minor groove of the DNA.The acridine-free TMPyP self-stacked on the DNA, and the binding mode was distinct that the binding was found to be achieved by the acridine intercalator.
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