Effect of Peptide Charge Distribution on the Structure and Kinetics of DNA Complex

Abstract

The complexes formed by DNA or siRNA interacting with polycations showed great potential as nonviral vectors for gene delivery. The physicochemical properties of the DNA/siRNA complexes, which could be tuned by adjusting the characteristics of polycations, were directly related to their performance in gene delivery. Using 21 bp double-stranded oligonucleotide (ds-oligo) and two icosapeptides (with the repeating units being KKGG and KGKG, respectively) of the same charge density as model molecules, we investigated the effect of charge distribution on the kinetics of complexation and the structure of the final complexes. Even though the distribution of the charged groups in peptides was only adjusted by one position, the complexes formed by (KKGG)5 and ds-oligo were larger in size and easier to precipitate than those formed by (KGKG)5. Counterintuitively, it was not the charged groups but the hydrophilic neutral spacers that determined the kinetics and the structure of the complex. We attributed such an effect to the water-mediated disproportionation process. The hydrophilic spacers next to each other were better than that in the separated pattern in holding water molecules after forming the complex. The water-rich domains in the complex functioned as a lubricant and facilitated the relaxation of the polyelectrolyte, resulting in a fast complexation process. The resulting complex was thus larger in size and lower in surface energy.