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A Rationally Designed Azobenzene Photoswitch for DNA G-Quadruplex Regulation in Live Cells
Marta Dudek1, Lucía López-Pacios2, Nasim Sabouri3
1Institute of Advanced Materials, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370, Wrocław, Poland.
Angewandte Chemie (International Ed. in English)
|September 13, 2024
Summary
Researchers developed a light-responsive G-quadruplex (G4) binder, Q-Azo4F-C, for precise cancer therapy. This compound dynamically controls G4 structures, leading to reversible cancer cell death and advancing precision medicine.
Area of Science:
- Biochemistry
- Chemical Biology
- Molecular Oncology
Background:
- G-quadruplex (G4) DNA structures are key targets in cancer research.
- Developing G4-specific compounds is crucial for precision cancer medicine.
Purpose of the Study:
- To create a light-responsive G4-binder for precise, spatiotemporal control of G4-associated cancer cell death.
- To investigate the dynamic regulation of G4 structures and their therapeutic potential.
Main Methods:
- Synthesis of a novel fluorinated azobenzene (AB) switch (Q-Azo4F-C) with quinoline and carboxamide moieties.
- Biophysical studies and molecular dynamics simulations to analyze ligand-G4 interactions.
- Cytotoxicity assays and immunostaining with G4 antibody (BG4) in cancer cell lines.
Main Results:
- Q-Azo4F-C exhibits distinct binding modes in trans and cis configurations.
- Over 25-fold reversible change in cytotoxic activity was observed between isomeric states.
- Demonstrated photo-driven, reversible regulation of G4 structures in lung cancer cells.
Conclusions:
- Light-responsive G4-binders offer dynamic control over G4 pathways for cancer therapy.
- Q-Azo4F-C shows potential for precision cancer treatment through spatiotemporal modulation of G4s.
