Redox-active daunomycin-spin-labeled nucleic acid complexes

Abstract

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.

Nucleic acid spin labeling study of interaction between polyadenylic acid: Polyuridilic acid duplex and egg phosphatidylcholine vesicles. Involvement of terminal and internal nucleotides and sugar-phosphate backbone

“…polynucleotides or DNA in the presence of phospholipid vesicles. A considerable number of papers were dedicated to the study of spin-labeled nucleic acids (e.g., see review papers [24][25][26], papers [27,28] and references therein), oligonucleofides [29] and nucleotides [30][31][32]. The main conditions for such work are site-specific spin labeling [27,28,30,31] and computer simulafion and convolution of EPR spectra of spin labeled polynucleotides.…”

“…A considerable number of papers were dedicated to the study of spin-labeled nucleic acids (e.g., see review papers [24][25][26], papers [27,28] and references therein), oligonucleofides [29] and nucleotides [30][31][32]. The main conditions for such work are site-specific spin labeling [27,28,30,31] and computer simulafion and convolution of EPR spectra of spin labeled polynucleotides. EPR technique and the use of specifically spin labeled DNA ate a tool for studying local dynamic properties of double and triple stranded nucleic acids [28,29], and for structural evaluation of s.s. sequences, mismatched base pairs, loops or Z-DNA [27].…”

“…The main conditions for such work are site-specific spin labeling [27,28,30,31] and computer simulafion and convolution of EPR spectra of spin labeled polynucleotides. EPR technique and the use of specifically spin labeled DNA ate a tool for studying local dynamic properties of double and triple stranded nucleic acids [28,29], and for structural evaluation of s.s. sequences, mismatched base pairs, loops or Z-DNA [27]. For EPR spectra of d.s.…”

“…For EPR spectra of d.s. high molecular mass poly¡ and DNA, the situation becomes more complicated since the experimental line shape depends both on dynamics of sugar-phosphate backbone (or/and heterocyclic bases) and intemal flexibility of spin label [27]. These polynucleotides cannot be anymore represented by a ffeely rotating cylinder.…”

“…These polynucleotides cannot be anymore represented by a ffeely rotating cylinder. Anisotropic motion of such spin labeled polynucleotides should be considered in terms of the Foufier transforms of correlation functions, with the values of the orientation-dependent rotational correlation time (rr and ~• calculated to be in the 20-100 ns region [27]. Nucleic acid spin labels have not been yet used for the study of nucleic acid-phospholipid interactions, though this technique could be promising for the above mentioned purpose.…”