Soluble Glycosaminoglycans Inhibit the Interaction of TAT−PTD with Lipid Vesicles |
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Authors: | Venkataswarup Tiriveedhi Peter Butko |
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Institution: | (1) Department of Chemistry & Biochemistry, University of Southern Mississippi, Hattiesburg, MS 39406, USA;(2) Present address: BRB 319, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA;(3) Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N. Pine St., PH 515, Baltimore, MD 21201, USA |
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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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Keywords: | Cell-penetrating peptides Glycosaminoglycans Membrane binding Fluorescence spectroscopy |
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