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Single-Molecule Fluorescence Visualization of DNA Polymerase Dynamics at G-Quadruplexes
Published on: April 4, 2025
Light-Controlled Folding and Chiroptical Sensing of G-Quadruplex DNA
Aleksandra Matusiak1, Jakub Trojnar1, Katarzyna Matczyszyn1
1Institute of Advanced Materials, Faculty of Chemistry Wrocław University of Science and Technology, Wyb. Wyspiańskiego 27, 50-370Wrocław, Poland.
The Journal of Physical Chemistry Letters
|August 13, 2026
Summary
This study introduces exAzoPy2, a novel photoswitch that uses visible light to control and sense G-quadruplex (G4) DNA structures. It reversibly modulates G4 folding and unfolds, enabling chiroptical discrimination of DNA states.
Area of Science:
- Molecular Biology
- Supramolecular Chemistry
- Photochemistry
Background:
- Controlling and sensing G-quadruplex (G4) DNA structures with photoswitches is challenging.
- Developing tools for reversible optical modulation of nucleic acid structures is crucial.
Purpose of the Study:
- To synthesize and characterize exAzoPy2, a visible-light-responsive photoswitch for G4 DNA.
- To investigate the isomer-dependent interaction of exAzoPy2 with G4 DNA topologies.
- To explore the potential of exAzoPy2 for chiroptical sensing of G4 DNA states.
Main Methods:
- Synthesis and photophysical characterization of exAzoPy2.
- Circular dichroism (CD) and fluorescence spectroscopy to study G4 DNA interactions.
- Investigation of isomer-dependent effects on G4 DNA folding and unfolding.
Main Results:
- exAzoPy2 exhibits isomer-dependent modulation of antiparallel G4 DNA structures.
- The cis isomer promotes G4 folding, while the trans isomer favors unfolding.
- exAzoPy2 generates distinct topology- and isomer-dependent induced circular dichroism (ICD) signals.
- ICD responses enable chiroptical discrimination of different G4 DNA conformations.
Conclusions:
- exAzoPy2 is a photoswitch capable of reversible optical control and structural sensing of G4 DNA.
- The photoswitch enables modulation of G4 DNA folding and unfolding.
- ICD signals provide a spectroscopic readout for distinguishing G4 DNA states.
