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Development of a Novel Light-up G-quadruplex Binding Compound

Research Project

Project/Area Number 18K05349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionChiba University

Principal Investigator

Keisuke iida  千葉大学, 大学院理学研究院, 助教 (70719773)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsグアニン四重鎖 / 核酸 / 蛍光化合物 / G4 / G4リガンド / 蛍光 / Light up / 蛍光検出 / AXL
Outline of Final Research Achievements

G-quadruplexes (G4s) are higher-order structures of nucleic acids formed from Hoogsteen base pairs in guanine-rich sequences. G4s regulate a wide variety of biological processes such as stress granule formation. G4-binding small molecules (G4 ligands) have been played a key role in the progress of this field. Notably, light-up G4 ligands whose fluorescence is selectively enhanced when interacting with G4s are useful for high-sensitivity detection. Herein, we present a fluorescent light-up probe with the ability to selectively stabilize G4s and enhance fluorescence upon G4 binding.
The foci of the probe were mainly observed in the nucleoli. These were co-localized with anti-fibrillarin antibodies and anti-G4 antibodies (BG4). Moreover, we tested detection of G4 in stress granules using the developed probe. We present a practical light-up probe for G4s in stress granules, providing potential targets for G4 ligands.

Academic Significance and Societal Importance of the Research Achievements

開発した化合物はG4に結合することで蛍光を発するLight-up型の蛍光化合物であることが明らかとなり、感度の高い検出を可能とした。これにより細胞内でG4の実用的なマーカーとして使用可能である。また、今回G4リガンドにより細胞を刺激するとストレス顆粒が誘導されることを明らかとしたが、これは新たなG4リガンドの薬理作用解明のための一助となる可能性がある。今後、化合物の更なる機能化の実装に加えて、ストレス顆粒中でのG4の働きを調査していくことで新たなG4による生体機能調節メカニズムが明らかになっていくことに期待する。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Destabilization of DNA and RNA G-quadruplex structures formed by GGA repeat due to N6-methyladenine modification2022

    • Author(s)
      Iwasaki Yuka、Ookuro Yurino、Iida Keisuke、Nagasawa Kazuo、Yoshida Wataru
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 597 Pages: 134-139

    • DOI

      10.1016/j.bbrc.2022.01.123

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topologies of G-quadruplex: Biological functions and regulation by ligands2020

    • Author(s)
      Ma Yue、Iida Keisuke、Nagasawa Kazuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: - Issue: 1 Pages: 3-17

    • DOI

      10.1016/j.bbrc.2019.12.103

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] (-)-Epigallocatechin gallate inhibits stemness and tumourigenicity stimulated by AXL receptor tyrosine kinase in human lung cancer cells2020

    • Author(s)
      Namiki Kozue、Wongsirisin Pattama、Yokoyama Shota、Sato Motoi、Rawangkan Anchalee、Sakai Ryo、Iida Keisuke、Suganuma Masami
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2444-2444

    • DOI

      10.1038/s41598-020-59281-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rif1 promotes association of G-quadruplex (G4) by its specific G4 binding and oligomerization activities2019

    • Author(s)
      Masai Hisao、Fukatsu Rino、Kakusho Naoko、Kanoh Yutaka、Moriyama Kenji、Ma Yue、Iida Keisuke、Nagasawa Kazuo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 8618-8618

    • DOI

      10.1038/s41598-019-44736-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Disulfide-Catalyzed Iodination of Electron-Rich Aromatic Compounds2019

    • Author(s)
      Iida Keisuke、Ishida Shunsuke、Watanabe Takamichi、Arai Takayoshi
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 84 Issue: 11 Pages: 7411-7417

    • DOI

      10.1021/acs.joc.9b00769

    • Related Report
      2019 Research-status Report
  • [Journal Article] Synthesis and Telomeric G-Quadruplex-Stabilizing Ability of Macrocyclic Hexaoxazoles Bearing Three Side Chains2019

    • Author(s)
      Ma Yue、Iida Keisuke、Sasaki Shogo、Hirokawa Takatsugu、Heddi Brahim、Phan Anh、Nagasawa Kazuo
    • Journal Title

      Molecules

      Volume: 24 Issue: 2 Pages: 263-263

    • DOI

      10.3390/molecules24020263

    • NAID

      120007133102

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Binding of a Telomestatin Derivative Changes Mechanical Anisotropy of Human Telomeric G-quadruplex2019

    • Author(s)
      Jonchhe, S.; Chimire, C.; Cui, Y.; Park, S.; Iida, K.; Nagasawa, K.; Sugiyama, H.; Mao, H.
    • Journal Title

      Angewandte Chemie international edition

      Volume: 58 Issue: 3 Pages: 877-877

    • DOI

      10.1002/anie.201811046

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Model studies for isolation of G-quadruplex-forming DNA sequences through a pull-down strategy with macrocyclic polyoxazole2019

    • Author(s)
      Iida Keisuke、Tsushima Yamato、Ma Yue、Sedghi Masoud Shadi、Sakuma Mai、Yokoyama Tomomi、Yoshida Wataru、Ikebukuro Kazunori、Nagasawa Kazuo
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 27 Issue: 8 Pages: 1742-1746

    • DOI

      10.1016/j.bmc.2019.02.056

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 2,6,7-Trisubstituted Prenylated indole2018

    • Author(s)
      Shiozawa Motoki、Iida Keisuke、Odagi Minami、Yamanaka Masahiro、Nagasawa Kazuo
    • Journal Title

      The Journal of Organic Chemistry

      Volume: in press Issue: 13 Pages: 7276-7280

    • DOI

      10.1021/acs.joc.7b03273

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth2018

    • Author(s)
      Rawangkan Anchalee、Wongsirisin Pattama、Namiki Kozue、Iida Keisuke、Kobayashi Yasuhito、Shimizu Yoshihiko、Fujiki Hirota、Suganuma Masami
    • Journal Title

      Molecules

      Volume: 23 Issue: 8 Pages: 2071-2071

    • DOI

      10.3390/molecules23082071

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular architecture of G-quadruplex structures generated on duplex Rif1-binding sequences2018

    • Author(s)
      Masai Hisao、Kakusho Naoko、Fukatsu Rino、Ma Yue、Iida Keisuke、Kanoh Yutaka、Nagasawa Kazuo
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 44 Pages: 17033-17049

    • DOI

      10.1074/jbc.ra118.005240

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of G-quadruplex ligands for selective induction of a parallel-type topology2018

    • Author(s)
      Ma Yue、Tsushima Yamato、Sakuma Mai、Sasaki Shogo、Iida Keisuke、Okabe Sachiko、Seimiya Hiroyuki、Hirokawa Takatsugu、Nagasawa Kazuo
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 16 Issue: 40 Pages: 7375-7382

    • DOI

      10.1039/c8ob01702f

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Visualization of Cellular G-quadruplexes using a Novel Fluorescent G-quadruplex Ligand2021

    • Author(s)
      Ayano Sasaki, Shunsuke Ishida, Takayoshi Arai, Keisuke Iida
    • Organizer
      The 48th International Symposium on Nucleic Acids Chemistry 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Structure-Activity Relationships of Cytotoxic Platinum(II)-Salphen Complexes as G-Quadruplex Ligands2021

    • Author(s)
      Natsumi Suzuki, Takayoshi Arai, Keisuke Iida
    • Organizer
      The 48th International Symposium on Nucleic Acids Chemistry 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] グアニン四重鎖 (G4) を蛍光検出する新規G4リガンドの開発2020

    • Author(s)
      石田 俊亮、荒井 孝義、飯田 圭介
    • Organizer
      日本化学会 第100春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ジスルフィドが促進する芳香族ヨウ素化反応の開発とその展開2019

    • Author(s)
      2)石田 俊亮、木村英嗣、飯田 圭介、渡邊 孝道、荒井 孝義
    • Organizer
      第78回有機合成化学協会関東支部シンポジウム -新津シンポジウム-
    • Related Report
      2019 Research-status Report
  • [Presentation] Recognition and Fluorescence Detection of G-quadruplex by ESIPT based ligand2019

    • Author(s)
      Keisuke Iida, Shunsuke Ishida, Ayano Sasaki
    • Organizer
      The 46th International Symposium on Nucleic Acids Chemistry
    • Related Report
      2019 Research-status Report
  • [Presentation] 大環状ヘキサオキサゾール誘導体を用いたグアニン四重鎖を標的とするLight-up型蛍光リガンドの創製2019

    • Author(s)
      若林 勇樹、馬 悦、飯田 圭介、齋藤 良太、長澤 和夫
    • Organizer
      日本ケミカルバイオロジー学会 第14回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ジスルフィド触媒による芳香族ヨウ素化反応2019

    • Author(s)
      石田 俊亮、飯田 圭介、渡邊 孝道、荒井 孝義
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] グアニン四重鎖を標的としたLight-up型蛍光リガンドの創製研究2019

    • Author(s)
      若林 勇樹、馬 悦、飯田 圭介、齋藤 良太、長澤 和夫
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Diphenyl Disulfide Catalyzed Iodination of Aromatic Compounds2019

    • Author(s)
      Keisuke Iida, Shunsuke Ishida, Takayoshi Arai
    • Organizer
      28th International Symposium on the Organic Chemistry of Sulfur
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] ジスルフィドを触媒とする芳香族ヨウ素化合物の製造方法2018

    • Inventor(s)
      荒井孝義、飯田圭介、石田俊亮
    • Industrial Property Rights Holder
      荒井孝義、飯田圭介、石田俊亮
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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