公开(公告)号：US5700677A

公开(公告)日：1997-12-23

申请号：US799769

申请日：1991-11-27

申请人： Roberto Crea ,  Roy Hoi Loi Pang ,  Hermann Oppermann ,  Peter C. Keck ,  Gabriel Alvarado-Urbina ,  Gay-May Wu ,  Charles M. Cohen

发明人： Roberto Crea ,  Roy Hoi Loi Pang ,  Hermann Oppermann ,  Peter C. Keck ,  Gabriel Alvarado-Urbina ,  Gay-May Wu ,  Charles M. Cohen

IPC分类号： C12N9/64 ,  A61K38/00 ,  A61K38/46 ,  A61P7/02 ,  C07K14/00 ,  C07K14/31 ,  C12N1/20 ,  C12N9/72 ,  C12N15/00 ,  C12N15/09 ,  C12P21/02 ,  C12R1/19 ,  A61K38/49 ,  C07K14/745

CPC分类号： C07K14/31 ,  C12N9/6459 ,  C12Y304/21069 ,  A61K38/00

摘要： Protein analogues of tissue plasminogen activator (tPA) are described. The analogues exhibit the proteolytic function of natural tPA and optionally fibrin binding activity, but are molecules, generally of lower molecular weight than natural tPA, designed for efficient expression in prokaryotic host cell systems. The analogues can comprise a catalytic fragment of tPA or a catalytic fragment of tPA linked to a polypeptide which stabilizes the catalytic fragment, provides for efficient expression of the fragment or confers a fibrin binding capability. Fibrin binding polypeptides can be a polypeptide fragments derived from tPA which embody the fibrin binding domain(s) of natural tPA or they can be an exogenous (non-tPA) polypeptides of eukaryotic or prokaryotic origin which exhibit fibrin binding affinity such as the antigen binding fragment of an antifibrin immunoglobulin or the B domain of protein A. Genetic constructs for expression of the analogues are also provided.

摘要翻译： 描述了组织纤溶酶原激活物（tPA）的蛋白质类似物。 类似物表现出天然tPA和任选的纤维蛋白结合活性的蛋白水解功能，但是通常具有比天然tPA低的分子量的分子，其设计用于在原核宿主细胞系统中有效表达。 类似物可以包含tPA的催化片段或与稳定催化片段的多肽连接的tPA的催化片段，提供片段的有效表达或赋予纤维蛋白结合能力。 纤维蛋白结合多肽可以是衍生自tPA的多肽片段，其表现为天然tPA的纤维蛋白结合结构域，或者它们可以是表现出纤维蛋白结合亲和力的真核或原核来源的外源（非tPA）多肽，例如抗原结合 抗纤维蛋白免疫球蛋白的片段或蛋白质B的B结构域。还提供了用于表达类似物的遗传构建体。