| Project/Area Number |
04403010
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
天然物有機化学
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SAITO Isao Kyoto University, Faculty of Engineering, Professor, 工学部, 教授 (20026082)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATANI Kazuhiko Kyoto University, Faculty of Engineering, Professor, 工学部, 助手 (70237303)
SUGIYAMA Hiroshi Kyoto University, Faculty of Engineering, Professor, 工学部, 助教授 (50183843)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 1994: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥20,300,000 (Direct Cost: ¥20,300,000)
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| Keywords | DNA Recognition / DNA Cleaver / Antitumor Antibiotics / Bleomycins / Neocarzinostatin / DNA Cleavage / DNA切断分子 / オリゴタクレオチド / DNA認識蛋白 / 人工制限酵素 / ハイブリッド蛋白 |
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| Research Abstract |
The aim of this research project is to design a novel biofuctional molecule targeted to DNA,based on the elucidation of the DNA cleavage mechanisms of naturally occuring DNA-Cleaving molecules.
1. Mechanistic Studies on the Action Mechanism of DNA-Cleaving Antitumor Antibiotics
Natural antitumor antibiotics such as bleomycin, neocarzinostatin, kaprimycin, or duocarmycins are known to cleavage DNA at specific sites. We are able to elucidate the mechanisms of DNA cleavage induced by bleomycins, neocarzinostatin and kapurimycins by using oligonucleotides as a DNA substrate. We have also succeeded to design a unique oligomer probe which has a radical clock at the target site. By using this novel oligomer, we were able to demonstrate for the first time that C-4' radical of deoxyribose residues is actually generated by the action of activated bleomycins.
2. Design of Sequence Specific DNA Cleavers
We have succeeded to design several important sequence specefic DNA cleavers which could find wide spread application in molecular biology and photobiology. One of the notable DNA cleavers is the -GG- specific DNA-cleaving molecule upon photostimulation. We also designed a practically useful DNA-cleaving amino acid which can be incorporated into the desired sites of DNA-binding polypeptides.
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