Abstract
Several models have been proposed for translocation of cell-penetrating peptides across membranes, but no general consensus on the mechanism of this process has emerged. It was hypothesized that heparan sulfate on the cell surface may play a role. We used fluorescence spectroscopy to study the effect of three soluble glycosaminoglycans—heparan sulfate, low-molecular-weight heparin, and dermatan sulfate—on the interaction of the fluorescently labeled peptide TAT−PTD with negatively charged small unilamellar vesicles. We found that the presence of glycosaminoglycans results in an order-of-magnitude increase in the apparent dissociation constant K d of the electrostatic component of the peptide/membrane interaction (from 0.13 to 2.6 mM). Thus, rather than aiding in the peptide’s penetration, soluble glycosaminoglycans competitively decrease TAT−PTD’s binding to the membrane, presumably by neutralizing its charge, and thereby attenuating electrostatic forces involved in the interaction. Our results, however, do not exclude a possible role of membrane-anchored glycosaminoglycans in the endocytotic transduction of CPPs across the cell membrane.
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Tiriveedhi, V., Butko, P. Soluble Glycosaminoglycans Inhibit the Interaction of TAT−PTD with Lipid Vesicles. Int J Pept Res Ther 14, 209–214 (2008). https://doi.org/10.1007/s10989-008-9131-6
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DOI: https://doi.org/10.1007/s10989-008-9131-6