Application of the Activated Reaction by Hybridization to Target Genes for the Regulation of Gene Expression in Cells

• Project/Area Number: 19350079
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Tohoku University
• Principal Investigator: NAGATSUGI Fumi Tohoku University, 多元物質科学研究所, 教授 (90208025)
• Co-Investigator(Kenkyū-buntansha): IMOTO Shuhei 東北大学, 多元物質科学研究所, 助教 (20447189)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2007: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: 核酸・蛋白質・糖化学 / クロスリンク反応 / クロスリンク / オリゴDNA / ペプチド核酸 / In Cell Chemistry / インベージョン / RNA標的 / 遺伝子発現制御 / ハイブリダイゼーション / 薬物放出システム

Research Abstract

本研究では遺伝子を標的とした選択的な化学反応により、細胞内における遺伝子機能を制御する方法、すなわち遺伝子を標的とするIn Cell Chemistryを提案し、その実現にむけた新しい分子の設計・合成、さらには細胞内における機能評価を行い、高機能を有する新規人工遺伝子制御分子の開発を目的とした。その方法論として我々が独自に開発したハイブリダイゼーション活性化反応を細胞内の遺伝子制御方法として展開することを目指し検討を行なった。その結果、非常に有効な方法論を開発できた

Research Products

• [Journal Article] Incorporation of an inducible nucleotide analog into DNA by DNA polymerases (2009)
  • Author(s): Md. M. Ali b, S. Imoto, Y. Li S. Sasaki F. Nagatsugi
  • Journal Title: Bioorg. Med. Chem. 17(In press)
  • Peer Reviewed
• [Journal Article] DNA Templated Click Chemistry for Creation of Novel DNA Binding Molecules (2008)
  • Author(s): Imoto S., Hirohama T., Nagatsugi F.
  • Journal Title: Bioorg. Chem. Lett. 18 Pages: 5660-5663
  • Peer Reviewed
• [Journal Article] Synthesis and Evaluation of the Luciferase-Oligodeoxynucleotide for the Sequences-Selective Detection of Nucleic Acids (2008)
  • Author(s): Nagatsugi F., Nakahara R., Inoue K., Sasaki S.
  • Journal Title: Arch. Pharm. Chem. Life Sci. 341 Pages: 562-567
  • Peer Reviewed
• [Journal Article] Synthesis of the Peptide Nucleic Acid(PNA)Incorporating 2-Amino-6-vinylpurine Derivative and Evaluation of the Reactivity (2008)
  • Author(s): Imoto S., Shimotazawa A., Goto M., Hirohama T., Nagatsugi F.
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 391-392
• [Journal Article] Synthesis of the new nucleoside analogue connecting 2-amino-6-vinylpurine to the 2'-deoxyribose skeleton via the methylene linker (2008)
  • Author(s): Kurose Y., Taniguchi Y., Nagatsugi F., Sasaki S.
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 391-392
• [Journal Article] New Methodology to Search for DNA Binding Ligands Based on Duplex DNA-Templated Click Chemistry (2008)
  • Author(s): Imoto S., Hirohama, T., Nagatsugi F.
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 381-382
• [Journal Article] DNA Templated Click Chemistry for Creation of Novel DNA Binding Molecules (2008)
  • Author(s): S. Imoto, T. Hirohama, F. Nagatsugi
  • Journal Title: Bioorg. Med. Chem. Lett. 18 Pages: 5660-5663
  • Peer Reviewed
• [Journal Article] Synthesis and Evaluation of the Luciferase-Oligodeoxynucleotide for the Sequences-Selective Detection of Nucleic Acids (2008)
  • Author(s): F. Nagatsugi, R. Nakahara, K. Inoue, S. Sasaki
  • Journal Title: Arch. Pharm. Chem. Life Sci., (2008) 341 Pages: 562-567
  • Peer Reviewed
• [Journal Article] Synthesis of the Peptide Nucleic Acid (PNA) Incorporating 2-Amino-6-vinylpurine Derivative and Evaluation of the Reactivity (2008)
  • Author(s): S. Imoto, A. Shimotazawa, M. Goto, T. Hirohama, F. Nagatsugi
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 391-392
• [Journal Article] Synthesis of the new nucleoside analogue connecting 2-amino-6-vinylpurine to the 2'-deoxyribose skeleton via the methylene linker (2008)
  • Author(s): Y. Kurose, Y. Taniguchi, F. Nagatsugi, S. Sasaki
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 43-44
• [Journal Article] New Methodology to Search for DNA Binding Ligands Basedon Duplex DNA-Templated Click Chemistry (2008)
  • Author(s): S. Imoto, T. Hirohama, F. Nagatsugi
  • Journal Title: Nucleic Acids Symp. Ser. 52 Pages: 381-382
• [Journal Article] Synthesis and Evaluation of the Peptide Nucleic Acids (PNAs) Incorporating Reactive Artificial Molecules (2008)
  • Author(s): S. Imoto, M. Goto, T. Hirohama, F. Nagatsugi
  • Journal Title: Collection symposium series (2008) 10 Pages: 414-416
• [Journal Article] Efficient Synthesis of 6-Substituted Purine Derivatives Using Pd-Catalyzed Cross-Coupling Reactions with 2'-Deoxyguanosine O^6-Tosylate (2007)
  • Author(s): Nagatsugi F.; Ogata, Y ; Imoto, S.; Sasaki, S.
  • Journal Title: Heterocycles 73 Pages: 493-501
  • NAID: 40015763816
  • Peer Reviewed
• [Journal Article] Enzymatic Incorporation of 2-amino-6-Vinylpurine Derivative (2007)
  • Author(s): Imoto, S.; Ali, M. M.; Li, Y.; Sasaki, S.; Nagatsugi, F.
  • Journal Title: Nucleic Acids Symp. Ser. 51 Pages: 357-358
• [Journal Article] Development of the Novel Drug Releasing System Triggered by Hybridization with Target Sequence (2007)
  • Author(s): Nagatsugi, F.; Nakayama, S.; Sasaki, S.
  • Journal Title: Nucleosides, Nucleotides Nucleic Acids 26 Pages: 799-803
  • Peer Reviewed
• [Journal Article] Efficient Synthesis of 6-Substituted Purine Derivatives Using Pd-Catalyzed Cross-Coupling Reactions with 2'-Deoxyguanosine Ο^6-Tosylate (2007)
  • Author(s): Nagatsugi F.
  • Journal Title: Heterocycles 73 Pages: 493-501
  • Peer Reviewed
• [Journal Article] Enzymatic Incorporation of 2-amino-6-Vinylpurine Derivative (2007)
  • Author(s): Imoto, S
  • Journal Title: Nucleic Acids Symp. Ser. 51 Pages: 357-358
• [Journal Article] Development of the Novel Drug Releasing System Triggered by Hybridization with Target Sequence, (2007)
  • Author(s): Nagatsugi, F.
  • Journal Title: Nucleosides, Nucleotides Nucleic Acids 26 Pages: 799-803
  • Peer Reviewed
• [Presentation] DNAの構造制御を目指したペプチド導入分子モーターの開発 (2009)
  • Author(s): 小林麻衣, 永谷直人, 桑原俊介, 永次史
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-29
• [Presentation] 分子モーターを組み込んだオリゴDNAの合成とその機能評価 (2009)
  • Author(s): 永谷直人, 桑原俊介, 原田宣之, 永次史
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-28
• [Presentation] RNA選択的クロスリンク剤の開発 (2009)
  • Author(s): 堀常晃, 井本修平, 萩原伸也, 永次史
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-28
• [Presentation] 反応性核酸を含むペプチド核酸(PNA)の合成と機能評価 (2009)
  • Author(s): 下田沢梓, 井本修平, 廣濱智哉, 後藤真, 永次史
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-28
• [Presentation] DNAの構造制御を目指した分子モーターの合成とその機能評価 (2009)
  • Author(s): 永次史, 永谷直人, 小林麻衣子, 桑原俊介
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-27
• [Presentation] 新しいバイオ技術開発に向けた機能分子の創製, 未来を切り拓く女性化学者たち (2008)
  • Author(s): 永次史
  • Organizer: 女性科学者が語る研究最前線
  • Place of Presentation: 北九州(invited)
  • Year and Date: 2008-12-17
• [Presentation] 2本鎖DNAの構造制御を目指した分子モーターの合成 (2008)
  • Author(s): 永次史
  • Organizer: 第11回生命化学研究会
  • Place of Presentation: 群馬
  • Year and Date: 2008-11-28
• [Presentation] RNA型クロスリンク剤の合成とその機能評価 (2008)
  • Author(s): 永次史, 堀常晃, 井本修平, 萩原伸也
  • Organizer: 第18回アンチセンスシンポジウム
  • Place of Presentation: 岐阜
  • Year and Date: 2008-11-18
• [Presentation] グアニンを標的とした新規クロスリンク剤の設計と合成 (2008)
  • Author(s): 服部恵一, 井本修平, 永次史
  • Organizer: 第34回反応と合成の進歩シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-11-15
• [Presentation] DNAの構造制御を目指した新規分子モーターの設計と合成 (2008)
  • Author(s): 小林麻衣子, 永谷直人, 桑原俊介, 永次史
  • Organizer: 第3回バイオ関連化学合同シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-09-19
• [Presentation] 遺伝子発現の選択的制御を目指した機能性分子の合成 (2008)
  • Author(s): 永次史
  • Organizer: 第2回機能性分子ミニシンポジウム
  • Place of Presentation: 筑波(invited)
  • Year and Date: 2008-09-11
• [Presentation] Synthesis of the Peptide Nucleic Acid(PNA)Incorporating 2-Amino-6-vinylpurine Derivative and Evaluation of the Reactivity (2008)
  • Author(s): S. Imoto, A. Shimotazawa, M. Goto, T. Hirohama, F. Nagatsugi
  • Organizer: Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids(IRTXVIII)and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kyoto
  • Year and Date: 2008-09-10
• [Presentation] Development of New DNA Binding Ligand Based on duplex DNA Templated Click Chemistry, Joint Symposium of 18th International Roundtable on Nucleosides (2008)
  • Author(s): T. Hirohama, S. Imoto, F. Nagatsugi
  • Organizer: Nucleotides and Nucleic Acids(IRTXVIII)and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kyoto
  • Year and Date: 2008-09-10
• [Presentation] Synthesis of the new nucleoside analogue connecting 2-amino-6-vinylpurine to the 2'-deoxyribose skeleton via the methylene linker, Joint Symposium of 18th International Roundtable on Nucleosides (2008)
  • Author(s): Y. Kurose., Y. Taniguchi, F. Nagatsugi, S. Sasaki
  • Organizer: Nucleotides and Nucleic Acids(IRTXVIII)and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Kyoto
  • Year and Date: 2008-09-10
• [Presentation] 遺伝子発現の選択的制御を目指した機能性分子の合成 (2008)
  • Author(s): 永次史
  • Organizer: 第2回機能性分子ミニシンポジウム
  • Place of Presentation: 筑波
  • Year and Date: 2008-09-10
• [Presentation] Development of New DNA Binding Ligand Based on duplex DNA Templated Click Chemistry (2008)
  • Author(s): S. Imoto, T. Hirohama, F. Nagatsugi
  • Organizer: Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids (IRTXVIII) and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: 京都
  • Year and Date: 2008-09-10
• [Presentation] Synthesis of the Peptide Nucleic Acid (PNA) Incorporating 2-Amino-6-vinylpurine Derivative and Evaluation of the Reactivity (2008)
  • Author(s): S. Imoto, A. Shimotazawa, M. Goto, T. Hirohama, F. Nagatsugi
  • Organizer: Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids (IRTXVIII) and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: 京都
  • Year and Date: 2008-09-10
• [Presentation] Synthesis of the new nucleoside analogue connecting 2-amino-6-vinylpurine to the 2'-deoxyribose skeleton via the methylene linker (2008)
  • Author(s): Kurose Y., Taniguchi Y., Nagatsugi F., Sasaki S
  • Organizer: Joint Symposium of 18th International Roundtable on Nucleosides, Nucleotides and Nucleic Acids (IRTXVIII) and 35th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: 京都
  • Year and Date: 2008-09-10
• [Presentation] Development of the New Strategies by Artificial Molecules for Regulation of Gene Expression (2008)
  • Author(s): Fumi Nagatsugi
  • Organizer: G-COE Sumer School
  • Place of Presentation: 仙台
  • Year and Date: 2008-08-18
• [Presentation] Development of the New Strategies by Artificial Molecules for Regulation of Gene Expression (2008)
  • Author(s): F. Nagatsugi
  • Organizer: G-COE Summer School
  • Place of Presentation: Sendai, Japan(invite)
  • Year and Date: 2008-08-17
• [Presentation] 遺伝子発現の選択的制御を目指した機能性分子の合成 (2008)
  • Author(s): 永次史
  • Organizer: 第20回, 生体機能関連化学若手の会
  • Place of Presentation: 白石(invited)
  • Year and Date: 2008-08-10
• [Presentation] 遺伝子発現の選択的制御を目指した機能性分子の合成 (2008)
  • Author(s): 永次史
  • Organizer: 第20回生体機能関連化学若手の会
  • Place of Presentation: 白石
  • Year and Date: 2008-08-10
• [Presentation] 応性ペプチド核酸の合成と機能評価 (2008)
  • Author(s): 下田沢梓, 井本修平, 廣濱智哉, 後藤真, 永次史
  • Organizer: 第20回生体機能関連化学若手の会
  • Place of Presentation: 白石
  • Year and Date: 2008-08-10
• [Presentation] DNAの構造制御を目指した分子モーター導入オリゴDNAの合成とその機能評価 (2008)
  • Author(s): 小林麻衣子, 永谷直人, 桑原俊介, 永次史
  • Organizer: 第20回生体機能関連化学若手の会
  • Place of Presentation: 白石
  • Year and Date: 2008-08-10
• [Presentation] 細胞内におけるDNA高次構造認識分子の開発 (2008)
  • Author(s): 永次史
  • Organizer: 第4回ライフサーベイヤシンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2008-06-26
• [Presentation] Synthesis and Evaluation of the Peptide Nucleic Acids(PNAs)Incorporating Reactive Artificial Molecules, XIV Symposium on Chemistry of Nucleic Acid Components (2008)
  • Author(s): S. Imoto, M. Goto, T. Hirohama, F. Nagatsugi
  • Organizer: Czesky Krumlov
  • Place of Presentation: Czech Republic
  • Year and Date: 2008-06-10
• [Presentation] Synthesis and Evaluation of the Peptide Nucleic Acids (PNAs) Incorporating Reactive Artificial Molecules (2008)
  • Author(s): S. Imoto, M. Goto, T. Hirohama, F. Nagatsugi
  • Organizer: XIV Symposium on Chemistry of Nucleic Acid Components
  • Place of Presentation: Czech Republic
  • Year and Date: 2008-06-10
• [Presentation] 誘起反応性クロスリンク核酸を用いた遺伝子配列特異的な薬物放出システムの開発 (2008)
  • Author(s): 永次史, 中山静香, 志茂祐輔, 井本修平, 佐々木茂貴
  • Organizer: 第3回ケミカルバイオロジー研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-20
• [Presentation] クリックケミストリーを応用した新規DNA結合分子探索手法の開発 (2008)
  • Author(s): 井本 修平
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 立教大学
  • Year and Date: 2008-03-28
• [Presentation] 反応性核酸塩基を組み込んだ新規ペプチド核酸の合成とその機能評価 (2008)
  • Author(s): 廣濱 智哉
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 立教大学
  • Year and Date: 2008-03-27
• [Presentation] 分子モーターを導入したオリゴDNAの合成とその機能評価 (2008)
  • Author(s): 永谷直人
  • Organizer: 日本化学会第88春季年会
  • Place of Presentation: 立教大学
  • Year and Date: 2008-03-26
• [Presentation] Application of the Inducible Reactive Oligonucleotides for Novel Drug Releasing System Triggered by Hybridization to Target Genes (2008)
  • Author(s): Fumi Nagatsugi
  • Organizer: The 1st International Symposium for "International Center of Research & Education for Molecular Complex Chemistry(IREMC)
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2008-03-13
• [Presentation] 反応性核酸を組み込んだペプチド核酸(PNA)の合成と反応性評価 (2007)
  • Author(s): 永次 史
  • Organizer: 第17回アンチセンスシンポジウム
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2007-12-04
• [Presentation] 細胞内における遺伝子配列特異的薬物放出システムの開発 (2007)
  • Author(s): 志茂祐輔
  • Organizer: 第7回多元物質科学研究所 研究発表会
  • Place of Presentation: 東北大学・片平さくらホール
  • Year and Date: 2007-12-03
• [Presentation] クロスリンク能を有する分子を導入したペプチド核酸の合成と評価 (2007)
  • Author(s): 後藤 真
  • Organizer: 第7回多元物質科学研究所 研究発表会
  • Place of Presentation: 東北大学・片平さくらホール
  • Year and Date: 2007-12-03
• [Presentation] Enzymatic Incorporation of 2-amino-6-Vinylpurine Derivative (2007)
  • Author(s): S.Imoto, M. M. Ali, Y. Li, S. Sasaki, F. Nagatsugi
  • Organizer: 5^<th> International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-11-21
• [Presentation] Enzymatic Incorporation of 2-amino-6-Vinylpurine Derivative (2007)
  • Author(s): Shuhei Imoto
  • Organizer: 5th International Symposium on Nucleic Acids Chemistry
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-11-21
• [Presentation] Development of the Novel Artificial Molecule for the Control of Gene Expression, (2007)
  • Author(s): Fumi Nagatsugi
  • Organizer: 7th Tateshina Conference on Organic Chemistry,
  • Place of Presentation: Tateshina, Japan
  • Year and Date: 2007-11-10
• [Presentation] DNAの構造制御を目指した新規分子モーター誘導体の合成と機能評価 (2007)
  • Author(s): 永谷直人
  • Organizer: 第33回反応と合成の進歩シンポジウム
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2007-11-06
• [Presentation] DNAの構造制御を目指した新規分子モーター誘導体の合成と物性 (2007)
  • Author(s): 桑原俊介
  • Organizer: 第22回生体機能関連化学シンポジウム
  • Place of Presentation: 東北大学・片平さくらホール
  • Year and Date: 2007-09-28
• [Presentation] DNAを鋳型とするクリックケミストリーを利用した新規DNA結合性ペプチドの開発 (2007)
  • Author(s): 井本修平
  • Organizer: 第22回生体機能関連化学シンポジウム
  • Place of Presentation: 東北大学・片平さくらホール
  • Year and Date: 2007-09-28
• [Presentation] Application of the Inducible Reactive Oligonucleotides for Novel Drug Releasing System Triggered by Hybridization to Target Genes (2007)
  • Author(s): F. Nagatsugi
  • Organizer: 4^<th> Japanese-Sino Symposium on Organic Chemistry for Young Scientists
  • Place of Presentation: Narita, Japan(invited)
  • Year and Date: 2007-09-26
• [Presentation] Application of the Inducible Reactive Oligonucleotides for Novel Drug Releasing System Triggered by Hybridization to Target Genes (2007)
  • Author(s): Fumi Nagatsugi
  • Organizer: 4th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
  • Place of Presentation: 成田
  • Year and Date: 2007-09-24
• [Presentation] Development of the Methodology for Searching New Binding Molecules to highly-Ordered DNA Structure (2007)
  • Author(s): F. Nagatsugi, S. Imoto
  • Organizer: The 2^<nd> International Workshop on Approaches to Single-cell Analysis
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2007-09-06
• [Presentation] Application of the Inducible Reactive Oligonucleotides for Novel Drug Releasing System Triggered by Hybridization (2007)
  • Author(s): F. Nagatsugi, S. Nakayma, S. Mori, S. Sasaki
  • Organizer: Gordon Conferences
  • Place of Presentation: New Port, USA
  • Year and Date: 2007-06-28
• [Presentation] 遺伝子配列特異的な薬物放出システムの開発 (2007)
  • Author(s): 中山静香
  • Organizer: 第18回万有仙台シンポジウム
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2007-06-23
• [Presentation] 細胞内における遺伝子配列特異的な薬物放出システムの開発 (2007)
  • Author(s): 永次 史
  • Organizer: 第2回ケミカルバイオロジー研究会
  • Place of Presentation: 京都大学時計台記念館
  • Year and Date: 2007-05-10
• [Presentation] 細胞内における化学的遺伝子発現制御を目指したアプローチ (2007)
  • Author(s): 永次史
  • Organizer: 東北大学学際科学国際高等研究センターフォーラム「生命科学における学際研究の最前線
  • Place of Presentation: 仙台(invited)
  • Year and Date: 2007-01-26
• [Presentation] 機能性人工核酸を用いた遺伝子発現制御による新しい創薬手法の開発 (2007)
  • Author(s): 永次史
  • Organizer: 第8回創薬ビジョンシンポジウム
  • Place of Presentation: 京都(invited)
  • Year and Date: 2007-01-25
• [Remarks] 永次史、機能性人工核酸を用いた遺伝子発現制御による新しい創薬手法の開発Pharma VISION NEWS, No.9, 24-28(2007)
• [Remarks] 永次史、遺伝子発現の化学的な制御を目指した人工分子の開発、ペプチド研究会レター、No.66, 4-6(2007)