| Project/Area Number |
09672289
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | SCIENCE UNIVERSITY OF TOKYO |
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Principal Investigator |
NAKAMURA Yushin SCIENCE UNIVERSITY OF TOKYO,Biologycal Science and Technology, Professor, 基礎工学部, 教授 (60118536)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Shigeki , 助手 (10287477)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | PSORALEN / PHOTOCROSS-LINKING / DNA CLEAVAGE / BLEOMYCIN MODEL / KB CELL / APOPTOSIS / プレオマイシンモデル / KB細胞 / DNA切断 |
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| Research Abstract |
The failure of bleomycin to cause mutagenesis may be a result of the killing of cells due to irreparable damage of DNA caused by highly double strand breaks. We designed a new type of DNA cleavage agent, iron complex-substituted psoralen (1) according to the following strategy and is essentially composed of following three parts : (A ) a moiety capable of photochemically cross-linking to DNA ; (B) a DNA cleaving moiety ; (C) a linker moiety connecting (A) and (B) having a high binding affinity to DNA.A psuralen was used as (A) , an iron-complexing group as cleaving moiety (B) which has been synthesized as a bleomycin model, and polymethylene-amides as a llnker (C). The photoreaction of which is noniron complex of 1, with Col El plasmld DNA gave the covalently interstrand cross - linked DNA which was caused the high double strand scissions in the presence of FeSO4 and dithiothreitol under air. The inhibision effect and apoptosis to KB cells of 1 were observed.
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