Redox-active daunomycin-spin-labeled nucleic acid complexes

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. Sa...

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Bibliographic Details
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
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00370a023