Cationic helicenes as selective G4 DNA binders and optical probes for cellular imaging

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• G-quadruplex DNA (G4 DNA) structures are increasingly recognized for their regulatory roles in biological processes.
• G4 DNA is a promising target for therapeutic drug development.
• Selective small molecule binders for G4 DNA are highly sought after.

Purpose of the Study:

• To investigate the interaction between helical compounds (helicenes) and G-quadruplex DNA (G4 DNA).
• To evaluate the selectivity of helicenes for G4 DNA compared to double-stranded DNA (dsDNA).
• To explore the potential of helicenes as fluorescent probes for cellular imaging.

Main Methods:

• Synthesis and characterization of novel helicene compounds.
• DNA binding studies using techniques to assess affinity and selectivity for G4 DNA versus dsDNA.
• Chiral recognition studies comparing enantiomers' interactions with different DNA topologies.
• Fluorescence spectroscopy to detect DNA binding and cellular imaging in U2OS cells.

Main Results:

• Non-planar helicenes exhibit reduced affinity for dsDNA compared to planar analogues, while maintaining high affinity for G4 DNA.
• Helicene enantiomers show differential recognition of chiral DNA environments in G4 and dsDNA.
• DNA binding induces a fluorescence switch-on effect in helicenes.
• Successful application of helicenes for cellular imaging of mitochondria and nuclei in live and fixed cells.

Conclusions:

• Helicenes are selective binders of G4 DNA, offering potential as therapeutic agents.
• The chiral nature of helicenes influences their DNA binding properties.
• The fluorescence switch-on capability makes helicenes valuable tools for biological imaging.
• Helicenes demonstrate promise for visualizing specific cellular compartments.