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 polynucleoti des-Calf Thymus DNA (C.T.DNA), poly(deoxyadenylic-deoxythymidylic acid) (te rmed Poly(AT)), poly(deoxyguanylic-deoxycytidylic acid) (termed Poly(GC)), and a double-stranded oligonucleotide of 12 base pairs (DNA-12mer)-were inv estigated by EPR. Computer-aided analysis of the EPR spectra provided infor mation on the mobility of the nitroxide labels and their partition in diffe rent environments, which, in turn, gave information on the interactions bet ween dendrimers and polynucleotides. After complexes were formed between DN A and SBD, the labels retained fast mobility at room temperature. On the ba sis of EPR analysis at 258 K, interaction of oligo- or polynucleotides with SBDs decreased in the following order: DNA-lamer > C.T.DNA > Poly(GC) > Po ly(AT). Small dendrimers (2SBD-T) at low pH (5.5) showed significant intera ction with the polynucleotides, which decreased with an increase in concent ration due to self-aggregation of dendrimer molecules. Conversely, interact ion between large dendrimers (6SBD-T) and polynucleotides increased with an increase in SBD concentration until saturation of the interacting sites oc curred. Comparison with previous studies on nSBD-T-vesicle systems indicate d that interaction of dendrimers with vesicles is stronger than dendrimer-p olynucleotide 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.