Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds.

Enhanced silencing and stabilization of siRNA polyplexes by histidine-mediated hydrogen bonds. Biomaterials. 2013 Oct 22; Authors: Chou ST, Hom K, Zhang D, Leng Q, Tricoli LJ, Hustedt JM, Lee A, Shapiro MJ, Seog J, Kahn JD, Mixson AJ Abstract Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We anticipate that elucidation of the binding mechanism of HK with siRNA will provide greater insight into the self-assembly and delivery of the HK:siRNA polyplex. Non-covalent bonds between histidine residues and nucleic acids may enhance the stability of siRNA polyplexes. We first compared the polyplex biophysical properties of a branched HK with those of branched asparagine-lysine peptide (NK). Consistent with siRNA silencing experiments, gel electrophoresis demonstrated that the HK siRNA polyplex maintained its integrity with prolonged incubation in serum, whereas siRNA in complex with NK was degraded in a time-dependent manner. Isothermal titration calorimetry of various peptides binding to siRNA at pH 7.3 showed that branched polylysine, interacted with siRNA was initially endothermic, whereas branched HK exhibited an exothermic reaction at initial binding. The exothermic interaction indicates formation of non-ionic bonds between histidines and siRNA; purely electrostatic interaction is entropy-driven and endothermic. To investigate the type of non-ionic bond, we studied the protonati...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research