Cell-penetrating compounds (CPCs) are commonly used to enhance the internalization of drugs, but their mechanism at the cell surface is poorly understood. We hypothesize that glycosaminoglycans (GAGs) play an integral role in the recognition and subsequent internalization of CPCs and their attached cargo. Here, the interactions of TAT peptide and G5 PAMAM dendrimer with four GAGs were studied through microcalorimetry to determine binding thermodynamics. Competitive displacement assays were used to quantify the concentration of each GAG needed to disrupt DNA complexes of both CPCs. Significant differences in affinity were seen, likely reflecting charge density and hydroxyl stereochemistry variations in GAG structure. These results lead to understanding the role these GAGs play in the cellular internalization of biomaterials, which will contribute to the design of systems with enhanced uptake ability and have implications in targeted delivery to a variety of cell types with different expression levels of these GAG receptors.

Structure affects glycosaminoglycan interaction with TAT peptide and G5 PAMAM dendrimer

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.