On the interpretation of Raman spectra of 1-aminooxy-spermine/DNA complexes

By FT-Raman spectroscopy, we have investigated the effect of 1-aminooxy-spermine (AOSPM) on aggregation and stability of calf-thymus DNA and selected oligonucleotide chains. AOSPM is able to mimic spermine in some macromolecular interactions, but is unable to substitute polyamines to maintain cell proliferation, suggesting pharmacological applications. Raman spectra of solutions containing AOSPM and either genomic DNA or two 15mer oligodeoxyribonucleotides, with GC or AT sequences, were recorded. Precipitation was observed for calf-thymus DNA, aggregated structures and appearance of several Z marker bands were observed for the 15mer GC sequence, and no macromolecular changes were detected for the 15mer AT sequence. Specific binding sites between the aminooxy group and the base residues were also evidenced. Assignment of the AOSPM Raman bands was supported on a normal mode calculation for the molecule NH2-O-CH3, as a model. The theoretical results, in combination with the analysis of the Raman bands, demonstrated that the aminooxy group played a relevant role in the AOSPM-DNA interaction. Preferential binding by the major groove was evidenced in the absence of macromolecular changes. When either precipitation or aggregation occurred, the interaction involved both the major and minor grooves. The specific interaction between AT/GC base pairs and the aminooxy group has also been theoretically investigated. The biological relevance of this work is discussed.