Effect of spermine conjugation on the interaction of acridine with alternating purine-pyrimidine oligodeoxyribonucleotides studied by CD, fluorescence and absorption spectroscopies.

ABSTRACT

We studied by electronic spectroscopies the interaction between double-stranded oligonucleotides containing either adenine-thymine or guanine-cytosine alternating sequences and N(1)-(acridin-9-yl)-1,16-diamino-4,8,13-triazahexadecane, which is a conjugated molecule formed by the covalent binding of spermine and 9-aminoacridine moieties via a trimethylene chain. Solutions containing the oligonucleotides and the conjugate, at different molar ratios, were studied by using electronic absorption, fluorescence emission and circular dichroism. Calculated association constants and fluorescence emission spectra showed that spermine conjugation induces sequence selectivity. The orientation of the intercalated acridine rings with respect to the oligonucleotide base planes was deduced from the electronic circular dichroism spectra. Evidence of the formation of spermine-induced aggregated structures, with potential applications to DNA packaging, gene therapy and anti-tumor therapy, was also achieved. Our data demonstrates that this spermine-acridine conjugate adds several specific characteristics provided by the polyamine moiety, as sequence selectivity, to the interesting properties of acridine derivatives.