[Interaction of the antineoplastic agent mitoxantrone with double-stranded nucleic acids]

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Context:

• Mitoxantrone is an anticancer agent.
• Understanding drug-nucleic acid interactions is crucial for drug development.
• Previous studies have suggested intercalation as the primary binding mode.

Purpose:

• To investigate the binding mechanism of mitoxantrone with double-helical DNA and RNA.
• To quantify binding stoichiometry and affinity under varying ionic strengths and temperatures.
• To elucidate the contributions of intercalation and electrostatic interactions to binding.

Summary:

• Mitoxantrone binds to double-helical DNA and RNA via intercalation and electrostatic interactions of its side chains.
• Binding stoichiometry is approximately 1:2-3 base pairs for DNA and 1:6-8 base pairs for RNA at 0.11 M NaCl.
• Binding enthalpy is approximately -(3.0 ± 0.5) kcal/mol, with affinity dependent on GC-content.

Impact:

• Provides detailed insights into mitoxantrone-nucleic acid interactions.
• Informs the design of novel anticancer agents with improved efficacy and reduced side effects.
• Contributes to the understanding of drug binding mechanisms to genetic material.