2009 Fiscal Year Final Research Report
Cell-biological analysis of sequence-specific DNA alkylating molecules.
| Project/Area Number |
20710164
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Living organism molecular science
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| Research Institution | Kyoto University |
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Principal Investigator |
KEN-ICHI Shinohara Kyoto University, 大学院・理学研究科, 助教 (70378561)
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| Co-Investigator(Renkei-kenkyūsha) |
BANDO Toshikazu 京都大学, 大学院・理学研究科, 准教授 (20345284)
SUGIYAMA Hiroshi 京都大学, 大学院・理学研究科, 教授 (50183843)
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| Project Period (FY) |
2008 – 2009
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| Keywords | テロメア / 核酸 / Py-Imポリアミド / 細胞老化 / DNAアルキル化 |
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| Research Abstract |
We designed and synthesized alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates. The effects on telomere shortening and growth inhibition were investigated using human cancer cell lines. In addition, we modified the DNA alkylating moiety CBI to the chlorambucil, which are easier to synthesize from commercially available components. The sequence-specific DNA alkylations by the chlorambucil conjugates were observed, which were as efficient as their of the CBI conjugates. The chlorambucil conjugates recognized 11 bp of telomere sequence specifically. However, the growth inhibiting activities were relatively reduced compared with CBI conjugates. Thus, these low-toxic and highly efficient DNA alkylating molecules should be more useful for investigation of their gene regulating activities and study of DNA-damage responses.
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