Creation and Pharmaceutical Development of Intelligent Zinc Fingers Based on Genomic Chemistry

• Project/Area Number: 20390037
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Doshisha Women's College of Liberal Arts
• Principal Investigator: SUGIURA Yukio Doshisha Women's College of Liberal Arts, 薬学部, 特任教授 (40025698)
• Co-Investigator(Kenkyū-buntansha): NEGI Shigeru 同志社女子大学, 薬学部, 助教 (50378866)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000); Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2008: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: 亜鉛フィンガー / 転写因子 / DNA結合 / タンパク質デザイン / マルチフィンガー / 人工転写因子 / 遺伝子制御 / Zif268 / マルチフインガー / GAGA因子

Research Abstract

By re-design of native zinc finger proteins, the following artificial proteins were created : (1) restriction enzyme-like molecule possessing DNA hydrolytic ability, (2) genome-regulating molecule with long DNA base recognition, and (3) metal-responsive artificial transcriptional switcher. The pharmaceutical application of these new proteins were investigated in this work.

Research Products

• [Journal Article] Zinc finger-zinc finger interaction between the transcription factors, GATA-1 and Spl, Biochem.Biophys. (2010)
  • Author(s): M.Imanishi, C.Imamura, C.Higashi, W.Yan, S.Negi, S.Futaki, Y.Sugiura
  • Journal Title: Res.Commun. 400(4) Pages: 625-630
  • Peer Reviewed
• [Journal Article] Metal-stimulated transcriptional regulation by an aritificial zinc finger protein (2010)
  • Author(s): M.Imanishi, T.Nakaya, T.Morisaki, D.Noshiro, S.Futaki, Y.Sugiura
  • Journal Title: ChemBioChem 11(12) Pages: 1653-1655
  • Peer Reviewed
• [Journal Article] マルチ亜鉛フィンガー型人工転写因子の創製と機能 (2010)
  • Author(s): 森崎達也、今西未来、二木史朗、杉浦幸雄
  • Journal Title: 薬学雑誌 130(1) Pages: 45-48
  • NAID: 130000152009
  • Peer Reviewed
• [Journal Article] Metal-stimulated transcriptional regulation by an artificial zinc finger protein (2010)
  • Author(s): M, Imanishi
  • Journal Title: ChemBioChem. Volume: 11 Pages: 1653-1655
  • Peer Reviewed
• [Journal Article] マルチ亜鉛フィンガー型人工転写因子の創製と機能 (2010)
  • Author(s): 森崎達也
  • Journal Title: 薬学雑誌 130 Pages: 45-48
  • Peer Reviewed
• [Journal Article] Novel zinc finger nuclease created by combining the Cys_2His_2 and His_4 type zinc finger domain (2009)
  • Author(s): S.Negi, Y.Umeda, S.Masuyama, Y.Sugiura
  • Journal Title: Bioorg.Med.Chem.Lett. 19(10) Pages: 2789-2791
  • Peer Reviewed
• [Journal Article] Novel zinc finger nuclease Created by combining the Cys_2His_2 and His_4 type zinc finger domains (2009)
  • Author(s): S.Negi
  • Journal Title: Bioorg.Med.Chem.Lett. 19 Pages: 2789-2791
  • Peer Reviewed
• [Journal Article] Effects of bulkiness and hydrophobicity of aliphatic amino acid at recognition helix of GAGA zinc finger on the stability of hydrophobic core and DNA-binding affinity (2008)
  • Author(s): M.Dhanasekaran, S.Negi, M.Imanishi, M.Suzuki, Y.Sugiura
  • Journal Title: Biochemistry 47(45) Pages: 11717-11724
  • Peer Reviewed
• [Journal Article] Rapid transcriptional activity in vivo and slow DNA binding in vitro by artificial multi-zinc finger protein (2008)
  • Author(s): T.Morisaki, M.Imanishi, S.Futaki, Y.Sugiura
  • Journal Title: Biochemistry 47(38) Pages: 10171-10177
  • Peer Reviewed
• [Journal Article] Novel redesigned zinc finger proteins : Design strategy and its application (2008)
  • Author(s): S.Negi, M.Imanishi, M.Matsumoto, Y.Sugiura
  • Journal Title: Chem.Eur.J. 14(11) Pages: 3236-3249
  • Peer Reviewed
• [Journal Article] Novel redesigned zinc finger proteins : Design strategy and its application (2008)
  • Author(s): S. Negi
  • Journal Title: Chem. Eur. J. 14 Pages: 3236-3249
  • Peer Reviewed
• [Journal Article] Rapid transcriptional activity in vivo and slow DNA binding invitro by artificial multi-zinc finger protein (2008)
  • Author(s): T. Morisaki
  • Journal Title: Biochemistry 47 Pages: 10171-10177
  • Peer Reviewed
• [Journal Article] Effects of bulkiness and hydrophobicity of aliphatic amino acid at recognition helix of GAGA zinc finger on the stability of hydrophobic core and DNA-binding affinity (2008)
  • Author(s): M. Dhanasekaran
  • Journal Title: Biochemistry 47 Pages: 11717-11724
  • Peer Reviewed
• [Presentation] インテリジェント人工亜鉛フィンガー蛋白質の創製と医学・薬学領域への展開 (2010)
  • Author(s): 杉浦幸雄
  • Organizer: 日本薬学会東海支部特別講演会
  • Place of Presentation: 名古屋市
  • Year and Date: 2010-11-04
• [Presentation] 亜鉛濃度に応答した亜鉛フィンガー転写因子の創製 (2010)
  • Author(s): 中屋智博、今西未来、森崎達也、能代大輔、二木史朗、杉浦幸雄
  • Organizer: 第20回金属が関与する生体関連反応シンポジウム
  • Place of Presentation: 徳島市
  • Year and Date: 2010-06-25
• [Presentation] リデザインによる野生型亜鉛フィンガータンパク質の機能改変:人工亜鉛フィンガー型ヌクレアーゼの創生 (2010)
  • Author(s): 根木滋、三間紘子、杉浦幸雄
  • Organizer: 第10回日本蛋白質科学会年会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-06-18
• [Presentation] 生体と金属:生体に不可欠な元素 (2009)
  • Author(s): 杉浦幸雄
  • Organizer: 第14回国際生物無機化学会議(公開市民講座)
  • Place of Presentation: 名古屋市
  • Year and Date: 2009-07-25
• [Presentation] 生体と金属-生体に不可欠な元素- (2009)
  • Author(s): 杉浦幸雄
  • Organizer: 第14回国際生物無機化学会議公開市民講座
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-07-25
• [Presentation] マルチ亜鉛フィンガー型人工転写因子の創製と機能 (2009)
  • Author(s): 森崎達也、今西未来、二木史朗、杉浦幸雄
  • Organizer: 第129回日本薬学会
  • Place of Presentation: 京都市
  • Year and Date: 2009-03-10
• [Presentation] マルチ亜鉛フィンガーのin vitro及びin celluloでの挙動相関 (2008)
  • Author(s): 森崎達也、今西未来、二木史朗、杉浦幸雄
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸市
  • Year and Date: 2008-12-09
• [Presentation] 新機能性人工亜鉛フィンガータンパク質の設計 (2008)
  • Author(s): 杉浦幸雄
  • Organizer: 第8回日本蛋白質科学会
  • Place of Presentation: 東京都
  • Year and Date: 2008-06-18
• [Presentation] 新機能性人工亜鉛フィンガー蛋白質の設計 (2008)
  • Author(s): 杉浦幸雄
  • Organizer: 第8回蛋白質科学会年会
  • Place of Presentation: タワーホール船橋(東京)
  • Year and Date: 2008-06-10
• [Book] Engineered Zinc Figer Proteins(Eds.by J.P.Mackey, D.J.Segal)(Non-FolkI-based zinc finger nucleases) (2010)
  • Author(s): M.Imanishi, S.Negi, Y.Sugiura
  • Publisher: Springer
• [Book] Engineered Zinc Finger Proteins (2010)
  • Author(s): M, Imanishi
  • Publisher: Springer Science