Soluble Glycosaminoglycans Inhibit the Interaction of TAT-PTD with Lipid Vesicles
Chemistry and Biochemistry
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.
International Journal of Peptide Research and Therapeutics
(2008). Soluble Glycosaminoglycans Inhibit the Interaction of TAT-PTD with Lipid Vesicles. International Journal of Peptide Research and Therapeutics, 14(3), 209-214.
Available at: http://aquila.usm.edu/fac_pubs/8985