Redox-active daunomycin-spin-labeled nucleic acid complexes

• Published in: Biochemistry (Easton) 1986-11, Vol.25 (22), p.6890-6895
• Main Authors: Ireland, John C, Pauly, Gary T, Bobst, Elizabeth V, Bobst, Albert M
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Applied sciences; Biological and medical sciences; Daunorubicin; DNA; Electron Spin Resonance Spectroscopy; Exact sciences and technology; General aspects; Medical sciences; Models, Molecular; Nucleic Acid Conformation; Other techniques and industries; Oxidation-Reduction; Pharmacology. Drug treatments; Polydeoxyribonucleotides; RNA; Spin Labels
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00370a023

Interaction studies between daunomycin (DM) and enzymatically spin-labeled nucleic acid duplexes reveal two modes of binding by electron spin resonance (ESR) spectroscopy. At a low drug/nucleotide (D/N) ratio, the drug binds in the intercalative mode with only a slight reduction in base mobility. Saturation in the intercalative mode is achieved at a lower D/N ratio for B' DNA than for B DNA. After full intercalation, further addition of DM seems to destabilize the helix and to allow the formation of redox-active DM stacks complexed to the nucleic acid lattice. These stacks will irreversibly oxidize all the nitroxides covalently bound to the 4- or 5-position of the pyrimidine base. Interactions between DM and spin-labeled single-stranded nucleic acids lead directly to the formation of redox-active complexes, while mixing of the drug with spin-labeled nucleic acid building blocks not incorporated in a nucleic acid lattice causes no ESR signal change. Complete disappearance of the ESR signal of spin-labeled nucleic acids extrapolates to a D/N value which is a constant for a particular lattice system and is independent of spin-labeling content.