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1. 发明申请

WO2011025957A3 TG-APROTININ FUSION PROTEINS AND MATRICES THEREOF 审中-公开
标题翻译： TG-APROTININ融合蛋白及其基因
公开(公告)号：WO2011025957A3
公开(公告)日：2011-07-07
申请号：PCT/US2010046991
申请日：2010-08-27
申请人： ECOLE POLYTECH , HUBBELL JEFFREY A , FREY PETER , LORENTZ KRISTEN
发明人： HUBBELL JEFFREY A , FREY PETER , LORENTZ KRISTEN
IPC分类号： A61L24/10
CPC分类号： A61L24/106 , A61L24/108 , A61L31/046 , A61L31/047
摘要： Fusion proteins containing a first domain and a second domain, where the first domain contains a crosslinkable substrate domain and the second domain contains a fibrinolysis inhibitor, are provided. In a preferred embodiment, the fibrinolysis inhibitor is a protease inhibitor, preferably, aprotinin. The fusion protein optionally contains a degradable site between the fist domain and the second domain. In a preferred embodiment, the crosslinkable substrate domain is a transglutaminase substrate domain, more preferably a Factor XIIIa substrate domain. Also provided is a method for decreasing the degradation of a fibrin matrix, and supplemented fibrin matrices with reduced degradation rates. The method includes covalently crossHnking a fusion protein containing a fibrinolysis inhibitor to the matrix. The supplemented fibrin matrices contain lower concentrations of a fibrinolysis inhibitor covalently bound to the matrix, compared to the concentration of unbound fibrinolysis inhibitor required to achieve the same reduction in degradation of the fibrin matrix.
摘要翻译：提供了含有第一结构域和第二结构域的融合蛋白，其中第一结构域含有可交联的底物结构域，第二结构域含有纤维蛋白溶解抑制剂。在优选的实施方案中，纤维蛋白溶解抑制剂是蛋白酶抑制剂，优选抑肽酶。融合蛋白任选地包含第一结构域和第二结构域之间的可降解位点。在优选的实施方案中，可交联底物结构域是转谷氨酰胺酶底物结构域，更优选因子XIIIa底物结构域。还提供了降低纤维蛋白基质降解的方法，以及降低降解速率的补充的纤维蛋白基质。该方法包括将含有纤维蛋白溶解抑制剂的融合蛋白共价交叉到基质上。与实现纤维蛋白基质降解相同的降低所需的未结合的纤维蛋白溶解抑制剂的浓度相比，补充的纤维蛋白基质含有较低浓度的与基质共价结合的纤维蛋白溶解抑制剂。

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