An EPR Study of the Interactions between Starburst Dendrimers and Polynucleotides

Interactions of nitroxide-labeled polyamidoamine dendrimers of generations 2 and 6 (2SBD-T and 6SBD-T, respectively) with double-stranded polynucleotidessCalf Thymus DNA (C.T.DNA), poly(deoxyadenylic-deoxythymidylic acid) (termed Poly(AT)), poly(deoxyguanylic-deoxycytidylic acid) (termed Poly(GC)), and a double-stranded oligonucleotide of 12 base pairs (DNA-12mer)swere investigated by EPR. Computer-aided analysis of the EPR spectra provided information on the mobility of the nitroxide labels and their partition in different environments, which, in turn, gave information on the interactions between dendrimers and polynucleotides. After complexes were formed between DNA and SBD, the labels retained fast mobility at room temperature. On the basis of EPR analysis at 258 K, interaction of oligoor polynucleotides with SBDs decreased in the following order: DNA-12mer > C.T.DNA > Poly(GC) > Poly(AT). Small dendrimers (2SBD-T) at low pH (5.5) showed significant interaction with the polynucleotides, which decreased with an increase in concentration due to self-aggregation of dendrimer molecules. Conversely, interaction between large dendrimers (6SBD-T) and polynucleotides increased with an increase in SBD concentration until saturation of the interacting sites occurred. Comparison with previous studies on nSBD-T-vesicle systems indicated that interaction of dendrimers with vesicles is stronger than dendrimer-polynucleotide interaction. This study provides some insights into dendrimer-DNA interactions of particular interest in understanding the mechanism of gene transfer to mammalian cells by SBDs.