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Updated: May 5, 2026
Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
Light-Activated Molecules Targeting G-Quadruplex Nucleic Acids
Marta Dudek1, Clément Cabanetos2, Marco Deiana1
1Institute of Advanced Materials, Faculty of Chemistry, Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370, Wrocław, Poland.
Abstract:
Phototherapies harness light's spatial and temporal precision to noninvasively modulate biomolecular interactions, providing a powerful platform for precision oncology. This approach is particularly effective in targeting disease-associated molecular structures such as G-quadruplexes (G4s), noncanonical nucleic acid conformations found in oncogene promoters and telomeres. These unique structures can impede DNA polymerase progression along the duplex, triggering DNA damage that ultimately compromises genomic stability. Stabilizing G4s with tailored ligands is currently being explored as a promising anticancer strategy, as it may induce toxic DNA damage specifically in rapidly dividing cancer cells. Unlike conventional G4 ligands, which remain continuously active, newly developed light-responsive molecules incorporate an OFF-ON switching mechanism that allows for spatiotemporal control over G4 dynamics and phototherapeutic effects. This concept article reviews a diverse array of light-responsive molecular tools, including photosensitizers (PSs), photocages, photochemically transformed ligands, and photoswitches, that selectively modulate G4-interactive binding properties, thereby laying the foundation for a versatile photopharmacological platform. Additionally, the article highlights recent advancements in this rapidly evolving field and discusses the challenges that remain for clinical translation, underscoring the significant potential of G4-targeted phototherapies to shape next-generation cancer treatments.
Insights
Light-responsive molecules offer precise control over G-quadruplexes (G4s) for cancer therapy. This photopharmacological approach enables targeted DNA damage in cancer cells, advancing precision oncology.
Area of Science:
- Oncology
- Photomedicine
- Molecular Biology
Background:
- G-quadruplexes (G4s) are noncanonical DNA structures in oncogenes and telomeres.
- G4 stabilization can induce DNA damage, a potential anticancer strategy.
- Current G4 ligands lack spatiotemporal control over their activity.
Purpose of the Study:
- To review light-responsive molecular tools for G4 modulation.
- To explore the potential of photopharmacology in precision oncology.
- To highlight advancements and challenges in G4-targeted phototherapies.
Main Methods:
- Review of photosensitizers, photocages, photochemically transformed ligands, and photoswitches.
- Discussion of light-responsive molecules for G4 interaction.
- Analysis of spatiotemporal control mechanisms.
Main Results:
- Light-responsive molecules offer OFF-ON switching for G4 modulation.
- These tools enable precise spatiotemporal control over G4 dynamics.
- A versatile photopharmacological platform for G4 targeting is established.
Conclusions:
- G4-targeted phototherapies represent a promising next-generation cancer treatment.
- Light-responsive molecules provide a novel strategy for precision oncology.
- Further research is needed for clinical translation of these G4-targeting approaches.
