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首页> 外文期刊>Acta biomaterialia >Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide
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Selective albumin-binding surfaces modified with a thrombin-inhibiting peptide

机译：凝血酶抑制肽修饰的选择性白蛋白结合表面

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Blood-contacting medical devices have been associated with severe clinical complications, such as thrombus formation, triggered by the activation of the coagulation cascade due to the adsorption of certain plasma proteins on the surface of biomaterials. Hence, the coating of such surfaces with antithrombotic agents has been used to increase biomaterial haemocompatibility. Biomaterial-induced clotting may also be decreased by albumin adsorption from blood plasma in a selective and reversible way, since this protein is not involved in the coagulation cascade. In this context, this paper reports that the immobilization of the thrombin inhibitor D-Phe-Pro-D-Arg-D-Thr-CONH 2 (fPrt) onto nanostructured surfaces induces selective and reversible adsorption of albumin, delaying the clotting time when compared to peptide-free surfaces. fPrt, synthesized with two glycine residues attached to the N-terminus (GGfPrt), was covalently immobilized onto self-assembled monolayers (SAMs) having different ratios of carboxylate-hexa(ethylene glycol)- and tri(ethylene glycol)-terminated thiols (EG6-COOH/EG3) that were specifically designed to control GGfPrt orientation, exposure and density at the molecular level. In solution, GGfPrt was able to inactivate the enzymatic activity of thrombin and to delay plasma clotting time in a concentration-dependent way. After surface immobilization, and independently of its concentration, GGfPrt lost its selectivity to thrombin and its capacity to inhibit thrombin enzymatic activity against the chromogenic substrate n-p-tosyl-Gly-Pro-Arg-p-nitroanilide. Nevertheless, surfaces with low concentrations of GGfPrt could delay the capacity of adsorbed thrombin to cleave fibrinogen. In contrast, GGfPrt immobilized in high concentrations was found to induce the procoagulant activity of the adsorbed thrombin. However, all surfaces containing GGfPrt have a plasma clotting time similar to the negative control (empty polystyrene wells), showing resistance to coagulation, which is explained by its capacity to adsorb albumin in a selective and reversible way. This work opens new perspectives to the improvement of the haemocompatibility of blood-contacting medical devices.
机译：与血液接触的医疗设备已与严重的临床并发症（例如血栓形成）相关联，这些并发症是由于某些血浆蛋白在生物材料表面上的吸附所引起的凝血级联反应的激活而触发的。因此，已经用抗血栓剂涂覆这样的表面，以增加生物材料的血液相容性。由于白蛋白以选择性和可逆的方式从血浆中吸附，因此也可以减少生物材料引起的凝血，因为该蛋白不参与凝血级联反应。在此背景下，本文报道了将凝血酶抑制剂D-Phe-Pro-D-Arg-D-Thr-CONH 2（fPrt）固定在纳米结构表面上可诱导白蛋白的选择性和可逆吸附，从而延迟了凝血时间不含肽的表面。将具有两个连接在N末端的甘氨酸残基的合成的fPrt共价固定在具有不同比例的羧酸酯-六（乙二醇）-和三（乙二醇）-末端硫醇的自组装单分子膜（SAMs）上（ EG6-COOH / EG3）是专为在分子水平上控制GGfPrt的方向，暴露和密度而设计的。在溶液中，GGfPrt能够以浓度依赖的方式失活凝血酶的酶活性并延迟血浆凝结时间。表面固定后，与浓度无关，GGfPrt失去了对凝血酶的选择性，失去了抑制凝血酶对生色底物n-对甲苯磺酰基-Gly-Pro-Arg-对硝基苯胺的酶活性。但是，低浓度GGfPrt的表面可能会延迟吸附的凝血酶裂解纤维蛋白原的能力。相反，发现以高浓度固定的GGfPrt诱导了吸附的凝血酶的促凝活性。但是，所有包含GGfPrt的表面的血浆凝结时间都与阴性对照（空的聚苯乙烯孔）相似，显示出对凝结的抵抗力，这是由其以选择性和可逆方式吸附白蛋白的能力解释的。这项工作为改善血液接触医疗设备的血液相容性开辟了新的前景。

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