| Project/Area Number |
08555228
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Synthetic chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SAITO Isao Kyoto University, Faculty of Engineering, Professor, 工学研究科, 教授 (20026082)
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| Co-Investigator(Kenkyū-buntansha) |
AOKI Toshi Fujisawa Medical Chemistry Research Laboratry, 新薬研究所, 研究員
NAKATANI Kazuhiko Kyoto University, Faculty of Engineering, Associate Professor., 工学研究科, 助教授 (70237303)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 1997: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1996: ¥6,400,000 (Direct Cost: ¥6,400,000)
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| Keywords | Kapurmycin A3 / DNA alkylation / guanine N7 / epoxide / cross-linking / DNA / 抗腫瘍性抗生物質 / オキシラニルメトキシアントランセン / メ-ジャーグループ |
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| Research Abstract |
The compound which effectively crosslink DNA is know to be a strong antitumor agent. We have envisioned to develop a novel antitumor agent by means of producing dimer of DNA alkylation agent showing antitumor activity. Antitumor antibiotic kapurimycin A_3 (1), ^1 having a structure closely related to pluramycin family, ^2 alkylates DNA by the attack of the epoxide subunit on the aguanine N7 to result in a formation of kapurimycin-DNA adduct, ^3 The high efficiency for the selective guanine N7 alkylation indicated that the epoxide subunit would be placed in the major groove of DNA with an appropriate alignment to the guanine N7 through a precovalent intercalation of the aromatic moiety. We have designed a "dimeric model" of kapurimycin A3 by means of introducing two epoxide moiety on anthracene structure. We have investigated synthesis of such compounds starting from 1,5-dihydroxyanthracene and 1,8-dihydroxyanthracene, but it turned out to be difficult to obtain proposed intermediate 1,5-dihydroxy-2,6-anthracenedialdehyde and 1,8-dihydroxy-2,7-anthracenedialdehyde. In contrast, simplified analog oxyranylmethoxyanthracene was found to be effective DNA alkylating agent with comparable reactivity with kapurimycin A3. We are now investigate a dimeric model of this compound.
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