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

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K05349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Chiba 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
• Keywords: グアニン四重鎖 / 核酸 / 蛍光化合物 / G4

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.

Free Research Field

ケミカルバイオロジー

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。