2009 Fiscal Year Final Research Report
Tailor-made Antitumor Agents based on DNA Sequence
| Project/Area Number |
17016033
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
SUGIYAMA Hiroshi Kyoto University, 大学院・理学研究科, 教授 (50183843)
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| Co-Investigator(Kenkyū-buntansha) |
BANDO Toshikazu 京都大学, 大学院・理学研究科, 准教授 (20345284)
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| Project Period (FY) |
2005 – 2009
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| Keywords | Py-Imポリアミド / テーラーメード抗がん剤 / 塩基配列認識 / 配列特異的アルキル化 / 遺伝子発現制御 |
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| Research Abstract |
Direct regulation of the expression level of a specific gene will provide a promising approach for cancer therapy. N-Methylpyrrole (Py) and N-methylimidazole (Im) polyamides are a new type of small molecules that precisely bind to the minor groove of the DNA duplex in a sequence-specific fashion. We designed and synthesized a series of sequence-specific alkylating Py-Im polyamide conjugates that selectively alkylate taget DNA sequences. We have demonstrated that sequence-specific alkylating agents possess gene-silencing activities and a promising potency against human cancer cell lines.
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[Journal Article] A Novel Gene Silence, Pyrrole-Imidazole Polyamide Targeting Human Lectin-like Oxidized Low-density Lipoprotein Receptor-1 Gene Improves Endothelial Cell Function.2009
Author(s)
Ueno, T.; Fukuda, N.; Tsunemi, A.; Yao, E.H.; Matsuda, H.; Tahira, K.; Matsumoto, T.; Matsumoto, Y.; Nagase, H.; Sugiyama, H.; Sawamura, T.
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Journal Title
J. Hypertens. 27
Pages: 508-516
Peer Reviewed
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[Journal Article] Requirement of β-Alanine Components in Sequence-Specific DNA Alkylation by Pyrrole-Imidazole Conjugates with Seven-Base Pair Recognition.2008
Author(s)
Bando, T.; Minoshima, M.; Kashiwazaki, G.; Shinohara, K.; Sasaki, S.; Fujimoto, J.; Ohtsuki, A.; Murakami, M.; Nakazono, S.; Sugiyama, H.
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Journal Title
Bioorg. Med. Chem. 16
Pages: 2286-2291
Peer Reviewed
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[Journal Article] A Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting LOX-1 Attenuates Restenosis of the Artery after Injury.2008
Author(s)
Yao, E-H.; Fukuda, N.; Ueno, T.; Matsuda, M.; Matsumoto, M.; Nagase, H.; Matsumoto, Y.; Takasaka, A.; Serie, K.; Sugiyama, H.; Sawamura, T.
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Journal Title
Hypertension 52
Pages: 86-92
Peer Reviewed
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[Journal Article] Development of Pyrrole-Imidazole Polyamide for Specific Regulation of Human Aurora Kinase A and B Gene Expression.2008
Author(s)
Takahashi, T.; Asami, Y.; Kitamura, E.; Suzuki, T.; Wang, X.; Igarashi, J.; Morohashi, A.; Shinojima, Y.; Kanou, H.; Saito, K.; Takasu, T.; Nagase, H.; Harada, Y.; Kuroda, K.; Watanabe, T.; Kumamoto, S.; Aoyama, T.; Matsumoto, Y.; Bando, T.; Sugiyama, H.; Yoshida-Noro, C.; Fukuda, N.; Hayashi N.
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Journal Title
Chem. Biol. 15
Pages: 829-841
Peer Reviewed
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[Journal Article] Development of Gene Silencing Pyrrole-Imidazole Polyamide Targeting the TGF-β1 Promoter for Treatment of Progressive Renal Diseases.2006
Author(s)
Matsuda, H.; Fukuda, N.; Ueno, T.; Tahira, Y.; Ayame, H.; Zhang, W.; Bando, T.; Sugiyama, H.; Saito, S.; Matsumoto, K.; Mugishima, H.; Serie, K.
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Journal Title
J. Am. Soc. Nephr. 17
Pages: 422-432
Peer Reviewed
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[Journal Article] Synthetic Pyrrole-Imidazole Polyamide Inhibits Expression of the Human Transforming Growth Factor-β1 Gene.2005
Author(s)
Lai, Y. -M.; Fukuda, N.; Ueno, T.; Kishioka, H.; Matsuda, H.; Saito, S.; Matsumoto, K.; Ayame, H.; Bando, T.; Sugiyama, H.; Mugishima, H.; Kim, S. -J.
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Journal Title
J. Pharmacol. Exp. Ther. 315
Pages: 571-575
Peer Reviewed
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