Aspirin-DNA interaction studied by FTIR and laser Raman difference spectroscopy

Area of Science:

• Molecular Biology
• Biochemistry
• Spectroscopy

Background:

• Aspirin is a widely used nonsteroidal anti-inflammatory drug.
• Understanding drug-DNA interactions is crucial for pharmacology and toxicology.
• Calf-thymus DNA is a common model for studying DNA-drug interactions.

Purpose of the Study:

• To investigate the interaction of aspirin with calf-thymus DNA in aqueous solution.
• To determine the binding sites, sequence preference, and structural changes of DNA upon aspirin complexation.
• To elucidate the molecular mechanisms of aspirin-DNA interaction at various drug concentrations.

Main Methods:

• Fourier transform infrared (FTIR) spectroscopy.
• Laser Raman difference spectroscopy.
• Vibrational spectroscopy to analyze drug binding sites and DNA structural alterations.

Main Results:

• At low aspirin concentrations, binding occurs primarily at the PO2 backbone and A-T base pairs, with minimal helix destabilization.
• At higher concentrations (r > 1/20), guanine and cytosine bases participate in binding, leading to partial helix destabilization.
• A significant structural shift from B-DNA to A-DNA conformation was observed upon aspirin complexation.
• Aspirin interacts via its CO and COOCH3 groups with DNA's PO2 and base donor sites.

Conclusions:

• Aspirin exhibits concentration-dependent binding to DNA, involving both backbone and base interactions.
• Aspirin complexation induces a conformational change in DNA structure from B-DNA to A-DNA.
• The study provides insights into the molecular interactions between aspirin and DNA, relevant for drug design and understanding cellular effects.