Perylene diimide G-quadruplex DNA binding selectivity is mediated by ligand aggregation.

Area of Science:

• Biochemistry
• Molecular Biology
• Supramolecular Chemistry

Background:

• G-quadruplex DNA structures are crucial in biological processes and are therapeutic targets.
• Perylene diimide (PDI) derivatives are investigated as potential G-quadruplex DNA binders.
• Ligand aggregation can significantly influence DNA binding affinity and selectivity.

Purpose of the Study:

• To investigate the pH-dependent aggregation of two N,N'-disubstituted perylene diimide ligands, PIPER and Tel01.
• To characterize how ligand aggregation affects G-quadruplex DNA binding selectivity.
• To understand the relationship between pH, ligand aggregation state, and DNA binding properties.

Main Methods:

• Visible absorbance spectroscopy to monitor ligand aggregation and DNA binding.
• Resonance light scattering to assess particle formation and aggregation.
• Fluorescence spectroscopy to study ligand-DNA interactions.
• Absorption spectroscopy to determine G-quadruplex DNA binding selectivity.

Main Results:

• Both PIPER and Tel01 ligands show pH-dependent aggregation.
• At low pH, ligands are not aggregated and bind to both duplex and G-quadruplex DNA.
• At higher pH, extensive ligand aggregation occurs, leading to high apparent G-quadruplex DNA binding selectivity.
• Spectroscopic methods confirmed the influence of pH on aggregation and binding.

Conclusions:

• The aggregation state of PIPER and Tel01 ligands is critically dependent on pH.
• Ligand aggregation significantly modulates the observed selectivity for G-quadruplex DNA.
• Understanding pH-dependent aggregation is essential for designing effective G-quadruplex DNA ligands.