The development of the functional polyamides to regulate specific DNA-protein structure

• Project/Area Number: 20611008
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Kyoto University
• Principal Investigator: BANDO Toshikazu Kyoto University, 大学院・理学研究科, 准教授 (20345284)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 機能性分子 / 合成化学 / 核酸

Research Abstract

We are utilizing pyrrole (Py)-imidazole (Im) polyamides to regulate DNA structures with DNA-protein interaction. By the progress of design, synthesis, and evaluation of the functional molecules, these studies demonstrated various types of functional Py-Im polyamides efficiently binding with covalent bond formation. In future, functional Py-Im polyamides which have high recognition against DNA sequences in the cell can be understood the regulating technology to specific gene expression.

Research Products

• [Journal Article] Potent Activity against K562 Cells by Polyamide-seco-CBI Conjugates Targeting Histone H4 Genes. Bioorg. (2010)
  • Author(s): Minoshima, M., Chou, J.C., Lefebvre, S., Bando, T., Shinohara, K., Gottesfeld, J.M., Sugiyama, H.
  • Journal Title: Med.Chem. 18 Pages: 168-174
• [Journal Article] Cell Permeability of Py-Im Polyamide-Fluorescein Conjugates : Influence of Molecular Size and Py/Im Content. (2010)
  • Author(s): Nishijima, S., Shinohara, K., Bando,T., Minoshima, M., Kashiwazaki, G., Sugiyama, H.
  • Journal Title: Bioorg.Med.Chem. 18 Pages: 978-983
• [Journal Article] Comparative Analysis of DNA Alkylation by Conjugates between Pyrrole-Imidazole Hairpin Polyamides and Chlorambucil or seco-CBI. (2010)
  • Author(s): Minoshima,M., Bando, T., Shinohara, K., Kashiwazaki, K., Nishijima, S., Sugiyama, H.
  • Journal Title: Bioorg.Med.Chem. 18 Pages: 1236-1243
  • NAID: 120001887644
• [Journal Article] A Chiral Wedge Molecule Inhibits Telomerase Activity. (2010)
  • Author(s): Shinohara, K., Sannohe, Y., Kaieda, S., Tanaka, K., Osuga, H., Tahara, H., Xu, Y., Kawase, T., Bando, T., Sugiyama, H.
  • Journal Title: J.Am.Chem.Soc. 132 Pages: 3778-3782
• [Journal Article] Alkylation of a Human Telomere Sequence by Heterotrimeric Chlorambucil PI Polyamide Conjugates. (2010)
  • Author(s): Kashiwazaki, G., Bando, T., Shinohara, K., Mioshima, M., Kumamoto, H. Nishijima, S., Sugiyama, H.
  • Journal Title: Bioorg med.chem. 18 Pages: 2887-2893
• [Journal Article] Potent Activity Against K562 Cells by Polyamide-seco-CBI Conjugates Targeting Histone H4 Genes (2010)
  • Author(s): Minoshima, M.; Bando, T.; Sugiyama, H.
  • Journal Title: Bioorg.Med.Chem. Volume: 18 Pages: 168-174
  • Peer Reviewed
• [Journal Article] Comparative Analysis of DNA Alkylation by Conjugates between Pyrrole-Imidazole Hairpin Polyamides and Chlorambucil or seco-CBI.Bioorg (2010)
  • Author(s): Minoshima, M.; Bando, T.; Sugiyama, H.
  • Journal Title: Bioorg.Med.Chem. Volume: 18 Pages: 1236-1243
  • Peer Reviewed
• [Journal Article] Alkylation of a Human Telomere Sequence by Heterotrimeric Chlorambucil PI Polyamide Conjugates (2010)
  • Author(s): Kashiwazaki, G.; Bando, T.; Sugiyama, H.
  • Journal Title: Bioorg.Med.Chem. Volume: 18 Pages: 2887-2893
  • Peer Reviewed
• [Journal Article] Cooperative alkylation of double-strand human telomere repeat sequences by PI polyamides with 11-base-pair recognition based on a heterotrimeric design, Bioorg. (2009)
  • Author(s): Kashiwazaki, G., Bando, T., Shinohara, K., Minoshima, M., Nishijima, S., Sugiyama, H.
  • Journal Title: Med.Chem. 17 Pages: 1393-1397
• [Journal Article] Development of a Molecule-Recognized Promoter DNA Sequence for Inhibition of HER2 Expression. (2009)
  • Author(s): Suzuki, T., Asami, Y., Takahashi, T., Wang, X., Watanabe, T., Bando, T., Sugiyama, H., Fukuda, N., Nagase, H.
  • Journal Title: J.Antibiot. 62 Pages: 339-341
  • NAID: 10030635628
• [Journal Article] Synthesis and Properties of Polyamide-SAHA Conjugate. (2009)
  • Author(s): Ohtsuki, A., Kimura, M.T., Minoshima, M., Suzuki, T., Ikeda, M., Bando, T., Nagase, H., Shinohara, K., Sugiyama, H.
  • Journal Title: Tetrahedron Lett. 50 Pages: 7288-7292
• [Journal Article] Cooperative alkylation of double-strand human telomere repeat sequences by PI polyamides with 11-base-pair recognition based on a heterotrimeric design (2009)
  • Author(s): G.Kashiwazaki, T.Bando^*, et. al.
  • Journal Title: Bioorg. Med. Chem. 17 Pages: 1393-1397
  • Peer Reviewed
• [Journal Article] Synthesis and Properties of Polyamide-SAHA Conjugate (2009)
  • Author(s): A.Ohtsuki, T.Bando, et. al.
  • Journal Title: Tetrahedron Lett. 50 Pages: 7288-7292
  • Peer Reviewed
• [Journal Article] Eukaryotic DNA Polymerases α, β and ε Incorporate Guanine Opposite 2, 2, 4-Triamino-5 (2H) -oxazolone (2009)
  • Author(s): K.Kino, T.Bando, et. al.
  • Journal Title: ChemBioChem 10 Pages: 2613-2616
  • Peer Reviewed
• [Journal Article] Sequence-Specific Alkylation by Y-shaped and Tandem Hairpin Pyrrole-Imidazole Polyamides (2008)
  • Author(s): Sasaki, S., Bando, T., Minoshima, M., Shinohara, K., Sugiyama, H.
  • Journal Title: Chem.Eur.J. 14 Pages: 864-870
• [Journal Article] Requirement of β-alanine components in sequence-specific DNA alkylation by pyrrole-imidazole conjugates with seven-base pair recognition, Bioorg. (2008)
  • Author(s): Bando, T., Minoshima, M., Kashiwazaki, G., Shinohara, K., Sasaki, S., Fujimoto, J., Ohtsuki, A., Murakami, M., Nakazono, S., Sugiyama, H.
  • Journal Title: Med.Chem. 16 Pages: 2286-2291
• [Journal Article] Pyrrole-Imidazole hairpin polyamides with high affinity at 5'-CGCG-3' DNA sequence; Influence of cytosine methylation on binding (2008)
  • Author(s): Minoshima, M., Bando, T., Sasaki, S., Fujimoto, J., Sugiyama, H.
  • Journal Title: Nucleic Acids Res. 36 Pages: 2889-2894
• [Journal Article] Detection of triplet repeat sequences in double-stranded DNA using pyrene-functionalized pyrrole-imidazole polyamides with rigid linkers, Bioorg. (2008)
  • Author(s): Fujimoto, J., Bando, T., Minoshima, M., Uchida, S., Iwasaki, M., Shinohara, K., Sugiyama, H.
  • Journal Title: Med.Chem. 16 Pages: 5899-5907
• [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.
  • Journal Title: Chem.Biol. 15 Pages: 829-841
• [Journal Article] Peryrene-Conjugated Pyrrole polyamides as a Sequence-specific Fluorescent Probe, Bioorg. (2008)
  • Author(s): Fujimoto, J., Bando, T., Minoshima,M., Kashiwazaki, G., Nishijima, S., Shinohara, K., Sugiyama, H.
  • Journal Title: Med.Chem. 16 Pages: 9741-9744
• [Journal Article] Sequence-Specific Alkylation by Y-shaped and Tandem Hairpin Pyrrole-Imidazole Polyamides (2008)
  • Author(s): Bando, T., Sugiyama H.
  • Journal Title: Chem. Eur. J. 18 Pages: 864-870
  • Peer Reviewed
• [Journal Article] Perylene-Conjugated Pyrrole Polyamide as a Sequence-Specific Fluorescent Probe (2008)
  • Author(s): Bando, T., Sugiyama, H
  • Journal Title: Bioorganic & Medicinal Chemistry 16 Pages: 9741-9744
  • Peer Reviewed
• [Journal Article] Requirement of b-Alanine Components in Sequence-Specific DNA Alkylation by Pyrrole-Imidazole Conjugates with Seven-Base Pair Recognition (2008)
  • Author(s): Bando, T., Sugiyama H.
  • Journal Title: Bioorganic & Medicinal Chemistry 16 Pages: 2286-2291
  • Peer Reviewed
• [Presentation] Recognition of Specific DNA Sequences by Pyrrole-Imidazole Polyamides (2010)
  • Author(s): 板東俊和
  • Organizer: 2010International Chemical Congress of Pacific Basin Societies(PACIFICHEM)
  • Place of Presentation: Hawaii, USA, December
• [Presentation] PIポリアミド-SAHAコンジュゲートライブラリによる細胞のリプログラミング (2010)
  • Author(s): 篠原憲一、板東俊和、杉山弘
  • Organizer: 日本ケミカルバイオロジー学会第5回年会
  • Place of Presentation: 横浜
• [Presentation] 配列特異的アルキル化を可能にする光切断リンカーを導入したPy-Imポリアミド-CBIコンジュゲート (2010)
  • Author(s): 朴昭映、板東俊和、杉山弘
  • Organizer: 日本化学会第90春季年会
  • Place of Presentation: 大阪
• [Presentation] Recognition of Specific DNA Sequences by Pyrrole-Imidazole Polyamides (2010)
  • Author(s): Bando, T.
  • Organizer: 2010 International Chemical Congress of Pacific Basin Societies(PACIFICHEM)
  • Place of Presentation: Hawaii
• [Presentation] 塩基配列特異的アルキル化能を有する機能性PIポリアミド設計 (2009)
  • Author(s): 板東俊和、杉山弘
  • Organizer: 第28回メディシナルケミストリーシンポジウム
  • Place of Presentation: 東京
• [Presentation] PIポリアミドコンジュゲートによる配列特異的DNAアルキル化反応 (2009)
  • Author(s): 板東俊和、蓑島維文、篠原憲一、杉山弘
  • Organizer: 第12回がん分子標的治療学会学術集会
  • Place of Presentation: 徳島
• [Presentation] 機能性PIポリアミドの合成とその機能評価 (2009)
  • Author(s): 板東俊和、蓑島維文、柏崎玄伍、西島茂樹、杉山弘
  • Organizer: 日本ケミカルバイオロジー学会第4回年会
  • Place of Presentation: 神戸
• [Presentation] DNAの配列特異的アルキル化と生物化学的応用 (2009)
  • Author(s): 蓑島維文、板東俊和、篠原憲一、杉山弘
  • Organizer: 日本化学会第89春季年会(2009)
  • Place of Presentation: 船橋市
• [Presentation] 機能性PIポリアミドの合成とその機能評価 (2009)
  • Author(s): 板東俊和
  • Organizer: 日本ケミカルバイオロジー学会 第4回年会
  • Place of Presentation: 神戸市産業振興センター
• [Presentation] 機能性ピロールーイミダゾールポリアミドによる特異的DNA塩基配列の検出 (2008)
  • Author(s): 板東俊和
  • Organizer: 第18回アンチセンスシンポジウム
  • Place of Presentation: 岐阜市
• [Presentation] 機能性PIポリアミドによる特異的DNA塩基配列確認 (2008)
  • Author(s): 板東俊和
  • Organizer: 学術フロンティア報告会
  • Place of Presentation: 東京
• [Presentation] テロメアを標的とするピロール-イミダゾールポリアミド (2008)
  • Author(s): 篠原憲一、蓑島維文、板東俊和、杉山弘
  • Organizer: 第12回がん分子標的治療研究会総会
  • Place of Presentation: 東京
• [Book] 基礎ケミカルバイオロジー (2011)
  • Author(s): 杉山弘, 板東俊和
  • Total Pages: 195
  • Publisher: 化学同人
• [Book] 基礎ケミカルバイオロジー (2011)
  • Author(s): 杉山弘、 板東俊和
  • Total Pages: 195
  • Publisher: 化学同人
• [Remarks] ホームページ等
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/
• [Remarks]
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/publication/
• [Remarks]
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/publication/all.html#2009
• [Remarks] 論文リスト
  • URL: http://kuchem.kyoto-u.ac.jp/chembio/Chenicalpage/publication2008.htm
• [Patent(Industrial Property Rights)] 標的遺伝子特異的ヒストン修飾制御剤 (2008)
  • Inventor(s): 永瀬浩喜, 板東俊和
  • Industrial Property Rights Holder: 学校法人日本大学
  • Industrial Property Number: 2008-172795
  • Filing Date: 2008-07-01