Unexpected DNA affinity and sequence selectivity through core rigidity in guanidinium-based minor groove binders

Area of Science:

• Medicinal Chemistry
• Biophysical Chemistry
• Molecular Biology

Background:

• DNA binders are crucial for molecular biology and drug development.
• Designing molecules with specific DNA sequence affinity is a key challenge.

Purpose of the Study:

• To design and synthesize novel rigid-core dicationic DNA binders.
• To evaluate their binding affinity and mode toward specific DNA sequences.

Main Methods:

• Surface Plasmon Resonance (SPR) and thermal denaturation for affinity evaluation.
• Circular Dichroism (CD) and UV-Vis spectroscopy for binding mode analysis.
• Density Functional Theory (DFT) calculations for result rationalization.

Main Results:

• Rigid-core dicationic compounds exhibit sequence-dependent DNA binding.
• Cation positioning significantly impacts binding strength.
• Fluorene derivatives show minor groove binding or intercalation; dihydroanthracene derivatives intercalate universally.

Conclusions:

• Novel fluorene and dihydroanthracene-based dicationic compounds are effective DNA binders.
• Molecular design can control DNA sequence specificity and binding modes.
• These compounds hold potential for applications requiring sequence-selective DNA interaction.