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 cell membrane glycosaminoglycans (GAGs) play an integral role in the recognition and subsequent internalization of CPCs and their attached cargo. Here, the interaction of one such CPC, TAT peptide, with four GAGs (heparin, heparan sulfate, dermatan sulfate and chondroitin sulfate A) was studied through microcalorimetry to determine binding constants, enthalpies and stoichiometries. 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.

Quantifying the interaction of TAT peptide and cell-surface glycosaminoglycans

243rd National Meeting (2012)

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