| Budget Amount *help |
¥4,240,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
In order to develop a novel strategy to control a gene expression, an olignnucleotidc-functional molecule conjugate has been synthesized and its biological properties were also studied. The results are summarized below.
1) Some heterocyclic compounds were designed, synthesized and incorporated into a bridged nucleic acid skeleton. The obtained bridged nucleic acids bearing unnatural nucleobases were also introduced into oligonucleotides, and their triplex-forming ability was investigated. Very interestingly, it was found that the recognition of pyrimicline-purine interruption site was successfully achieved by the bridged nucleic acid derivatives /
2) As a convenient method to introduce a functional group into oligonucleotides, a post-elongation modification method based on Click chemistry was developed. Furthermore, some oligonucleotides conjugated with a transcription factor-binding site (double stranded DNA) were also successfully prepared.
3) The oligonucleotides bearing unnatrural nucleobases prepared above were transfected into living cells, and their ability to control gene expression was evaluated. The oligonucleotides bearing unnatural nucleobases, by themselves or together with the antigene-block strategy developed by our group, showed effective regulation of gene expression. Furthermore, the oligonucleotides conjugated with a transcription factor-binding site promoted the target gene expression. These results are of great interest and would be useful for further biological application.
4) A relationship between chemical structures of oligonucleotide analogues and their triplex-forming ability was evaluated in detail, and the novel bridged nucleic acid, of which triplex-forming ability was higher than that of the pinto-type BNA, was successfully developed.
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