Immobilization of the irreversible thrombin inhibitor D-Phe-Pro-Arg-chloromethylketone: A concept for hemocompatible surfaces?
Immobilization of the irreversible thrombin inhibitor D-Phe-Pro-Arg-chloromethylketone: A concept for hemocompatible surfaces?
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DOI：
10.1002/jbm.a.32780
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Werner, Carsten
中科院分区：
文献类型：
--
作者：
Maitz, Manfred F.;Sperling, Claudia;Werner, Carsten
不可逆凝血酶抑制剂 D-Phe-Pro-Arg-氯甲基酮 (PPACK) 在其伯氨基处共价固定到聚乙二醇化聚合物薄膜上。放射性缀合凝血酶的活性测定和捕获表明，PPACK 修饰的表面可以结合凝血酶，形成高达 30% 的单层密度。这种高凝血酶抑制能力的反算表明，抑制剂的表面固定仍然与两个以上数量级的活性损失有关；在较高的表面密度下观察到活性增加。与不含抑制剂的参考基材相比，含 PPACK 的聚合物薄膜的血浆凝固时间几乎延长了一倍。然而，在全血中，其抗凝特性低于之前发现的苯甲脒型可逆凝血酶抑制剂的抗凝特性；此外，表面表现出炎症特性。结论是，固定化可逆凝血酶抑制剂通过与抗凝血酶 III 协同作用钝化更多量的凝血酶而更有效。 (C) 2010 Wiley periodicals, Inc. J Biomed Mater Res Part A: 94A: 905-912, 2010
The irreversible thrombin inhibitor D-Phe-Pro-Arg-chloromethylketone (PPACK) was covalently immobilized to PEGylated polymer thin films at its primary a-amino group. Activity assays and capture of radioconjugated thrombin reveal that the PPACK-decorated surfaces could bind thrombin forming up to 30% of a monolayer density. Back-calculation of this high thrombin-inhibiting capacity indicated that the surface immobilization of the inhibitor was still associated with more than two orders of magnitude of loss of activity; increasing activity was observed at higher surface densities. PPACK-containing polymer films almost duplicated the plasma coagulation time when compared with the reference substrate without inhibitor. In whole blood, however, the anticoagulant properties were below those previously found for benzamidine-type reversible thrombin inhibitors; in addition, the surface exhibited inflammatory properties. It is concluded that immobilized reversible thrombin inhibitors are more effective by passivating higher amounts of thrombin in a cooperative action with antithrombin III. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 94A: 905-912, 2010