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Click-Chemistry-Based Biomimetic Ligands Efficiently Capture G-Quadruplexes In Vitro and Help Localize Them at DNA
Francesco Rota Sperti1, Baptiste Dupouy1, Jérémie Mitteaux1
1Institut de Chimie Moléculaire, ICMUB CNRS UMR 6302, UBFC Dijon, 21078 Dijon, France.
JACS Au
|August 1, 2022
Summary
Researchers developed BioTriazoTASQ, a versatile molecular tool for studying G-quadruplex (G4) structures in human cells. This ligand efficiently isolates G4s and reveals their role in DNA damage, advancing G4 chemical biology.
Area of Science:
- Chemical Biology
- Molecular Biology
- Genomics
Background:
- G-quadruplex (G4) structures play crucial roles in cellular processes.
- Investigating G4 biology requires sophisticated molecular tools.
- Existing tools may have limitations in accessibility and versatility.
Purpose of the Study:
- To develop a versatile and chemically accessible G4 ligand for G4-focused chemical biology.
- To utilize the ligand for isolating and identifying G4s from DNA and RNA.
- To investigate the role of ligand-stabilized G4s in DNA damage in human cells.
Main Methods:
- Design and synthesis of a biotinylated G4 ligand (TASQ) using click chemistry.
- Affinity purification protocols to isolate DNA and RNA G4s.
- Optical imaging techniques to visualize G4 localization and DNA damage foci.
Main Results:
- A novel biotinylated, triazole-assembled TASQ (BioTriazoTASQ) was efficiently synthesized.
- BioTriazoTASQ successfully isolated both DNA and RNA G4s from solution.
- Ligand-stabilized G4 sites were shown to colocalize with DNA damage foci in human cells.
Conclusions:
- BioTriazoTASQ is a versatile tool for G4 chemical biology investigations.
- The ligand facilitates the isolation and identification of G4 structures.
- G4 structures are strategically relevant and contribute to DNA damage in human cells.
