Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence...

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Triplex DNA structures are key targets for gene inhibition in diseases like cancer.
• Coralyne is a DNA-targeting drug with known affinity for triplex DNA.
• Understanding coralyne-triplex interactions is crucial for developing gene-targeting therapeutics.

Purpose of the Study:

• To investigate the binding mechanisms of coralyne with typical triplex DNA structures.
• To elucidate how coralyne binding affects triplex DNA stability and sequence recognition.
• To explore the potential of coralyne-triplex interactions in anti-gene therapeutics.

Main Methods:

• Combined steady-state and ultrafast fluorescence spectroscopy.
• Photoinduced electron transfer (PET) analysis to study coralyne-DNA interactions.
• Distinguished monomeric intercalation and aggregate stacking binding modes.

Main Results:

• Coralyne fluorescence is quenched by photoinduced electron transfer (PET) with guanine bases in triplex DNA.
• PET rates reveal sensitivity to binding configuration and microenvironment, distinguishing binding modes.
• Coralyne shows sequence-specific binding: monomeric intercalation in CGG and TAT triplexes, aggregate stacking in CGC+ triplex due to charge repulsion.
• Coralyne aggregation acts as a probe for local DNA water content.
• Intercalated coralyne monomers stabilize triplex structures via π-π stacking.

Conclusions:

• Coralyne exhibits sequence-specific binding to triplex DNA, involving distinct monomeric and aggregate modes.
• These interactions provide mechanistic insights into coralyne's triplex-binding propensity.
• Coralyne-triplex interactions hold promise for developing targeted anti-gene therapeutics.