The complexes formed by DNA or siRNAinteracting with polycationsshowed great potential as nonviral vectors for gene delivery. Thephysicochemical properties of the DNA/siRNA complexes, which couldbe tuned by adjusting the characteristics of polycations, were directlyrelated to their performance in gene delivery. Using 21 bp double-strandedoligonucleotide (ds-oligo) and two icosapeptides (with the repeatingunits being KKGG and KGKG, respectively) of the same charge densityas model molecules, we investigated the effect of charge distributionon the kinetics of complexation and the structure of the final complexes.Even though the distribution of the charged groups in peptides wasonly adjusted by one position, the complexes formed by (KKGG)5and ds-oligo were larger in size and easier to precipitatethan those formed by (KGKG)5. Counterintuitively, it wasnot the charged groups but the hydrophilic neutral spacers that determinedthe kinetics and the structure of the complex. We attributed suchan effect to the water-mediated disproportionation process. The hydrophilicspacers next to each other were better than that in the separatedpattern in holding water molecules after forming the complex. Thewater-rich domains in the complex functioned as a lubricant and facilitatedthe relaxation of the polyelectrolyte, resulting in a fast complexationprocess. The resulting complex was thus larger in size and lower insurface energy. [ABSTRACT FROM AUTHOR]