| Project/Area Number |
15510180
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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 |
Living organism molecular science
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
TOSHIMA Kazunobu KEIO UNIVERSITY, FACULTY OF SCIENCE AND TECHNOLOGY, PROFESSOR, 理工学部, 教授 (60217502)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | DNA / PHOTOCLEAVAGE / ANTHRACENE / BULGE DNA / CARBOHYDRATE / TELOMERASE / ETHIDUIM BROMIDE / ANTICANCER AGENT / G-カルテット / 阻害剤 / 抗ガン剤 / 誘導体 / フェナントリジン / DNA点変異 / 核酸塩基 / ハイブリッド / DNA融解温度 / 抗細胞活性 |
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| Research Abstract |
In this study, the following three main projects were carried out. 1)Novel DNA photocleaving agents possessing a hybrid structure of anthracene and deoxyamino sugar were developed. Thus, it was found that novel designed hybrids having anthracene and deoxyamino sugar as a DNA intercalator and a DNA groove binder, respectively, selectively cleaved double stranded DNA at the guanine site under the photoirradiation using a long wave-length UV without any additives. Furthermore, these agents were found to show strong cytotoxicity against cancer cells under the photoirradiation. 2)Novel bulge DNA recognition molecules were developed. Thus, the designed hybrid possessing cytosine and carbohydrate was synthesized via an effective glycosidation reaction, and found to selectively recognize and stabilize G-bulged DNA while complementally DNA and A-,C- and T-bulged DNAs were not recognized by the hybrid. These results clearly showed that the designed hybrid was very useful for detecting the G-bulged DNA. 3)Novel telomerase inhibitors were also developed. Thus, several derivatives were designed and synthesized based on the structure of ethidium bromide which was known to interact with G-quartet structure of DNA and exhibit telomerase inhibiting activity. It was found that the amino groups at the C3 and C8 positions and the quarternarization of the N-5 position of ethidium bromide were essential for its telomerase inhibiting activity. Furthermore, it was demonstrated that methyl group is more effective than ethyl group at the N-5 position of ethidium bromide for its telomerase inhibiting activity. These results gave significant information for designing novel telomerase inhibitors based on ethidium bromide structure.
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