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首页> 外文期刊>International Journal of Peptide Research and Therapeutics >Soluble Glycosaminoglycans Inhibit the Interaction of TAT?PTD with Lipid Vesicles
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Soluble Glycosaminoglycans Inhibit the Interaction of TAT?PTD with Lipid Vesicles

机译：可溶性糖胺聚糖抑制TAT？PTD与脂质囊泡的相互作用

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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.
机译：已经提出了几种用于细胞穿透肽跨膜转运的模型，但是尚未出现关于该过程机理的普遍共识。假设细胞表面的硫酸乙酰肝素可能起作用。我们使用荧光光谱研究了三种可溶性糖胺聚糖（硫酸乙酰肝素，低分子量肝素和硫酸皮肤素）对荧光标记的肽TAT？PTD与带负电的单层小囊泡相互作用的影响。我们发现糖胺聚糖的存在导致肽/膜相互作用的静电成分的表观解离常数K dsub的数量级增加（从0.13到2.6 mM）。因此，大概是通过中和其电荷，可溶性糖胺聚糖竞争性地降低了TAT？PTD与膜的结合，而不是辅助肽的渗透，从而减弱了相互作用中涉及的静电力。然而，我们的结果并未排除膜锚定的糖胺聚糖在跨细胞膜的CPP内吞转导中的可能作用。

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