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    • 4. 发明申请
    • CLONING AND PRODUCTION OF POLYPEPTIDE ANALOGS OF HUMAN FIBRONECTIN AND METHOD OF USING SUCH POLYPEPTIDE ANALOGS
    • 克隆和生产人类纤维蛋白的多肽类似物和使用这种多肽类似物的方法
    • WO1990007577A1
    • 1990-07-12
    • PCT/US1989005875
    • 1989-12-29
    • BIO-TECHNOLOGY GENERAL CORP.VOGEL, TikvaLEVANON, AvigdorWERBER, MosheGUY, RachelPANET, Amos
    • BIO-TECHNOLOGY GENERAL CORP.
    • C12N15/12
    • C07K19/00A61K38/00A61K49/0002A61K49/0004A61K49/0008A61K2123/00A61M25/0045C07K14/78
    • This invention provides plasmids for bacterial expression of polypeptides which comprise a substantial portion of the amino acid sequence of, and which have the biological activity of, one of the domains of naturally-occurring human fibronectin, such as the cell binding domain or fibrin binding domain, comprising DNA encoding the polypeptide and DNA encoding suitable regulatory elements positioned relative to the DNA encoding the polypeptide so as to effect expression of the polypeptide in a suitable host cell. In the presently preferred embodiments of the invention, the polypeptide is a 75 kD, 40 kD or 33 kD polypeptide of the cell binding domain, or a 31 kD or 20 kD polypeptide of the fibrin binding domain. The invention also provides methods for producing the polypeptides and pharmaceutical compositions comprising the polypeptides and pharmaceutically acceptable carriers. The polypeptides of this invention may be used to inhibit platelet aggregation, to inhibit thromboxane release from platelets, or to treat a subject with a cerebrovascular disorder, a cardiovascular disorder, a wound, a bacterial infection, a cancer, or to detect a fibrin thrombi. The invention further provides the polypeptides conjugated to thrombolytic agents, growth factors, serum albumin, blood factors, or polyethyleneglycol.
    • 本发明提供用于细菌表达多肽的质粒,其包含大部分天然存在的人纤连蛋白结构域之一的氨基酸序列的氨基酸序列,并且具有生物学活性,例如细胞结合结构域或纤维蛋白结合结构域 ,其包含编码所述多肽的DNA和编码相对于编码所述多肽的DNA定位的合适的调节元件的DNA,以便实现所述多肽在合适的宿主细胞中的表达。 在本发明目前优选的实施方案中,多肽是细胞结合结构域的75kD,40kD或33kD多肽,或纤维蛋白结合结构域的31kD或20kD多肽。 本发明还提供了生产多肽的方法和包含多肽和药学上可接受的载体的药物组合物。 本发明的多肽可用于抑制血小板聚集,抑制血小板从血小板释放或治疗患有脑血管障碍,心血管疾病,伤口,细菌感染,癌症的受试者,或用于检测血纤维蛋白血栓 。 本发明还提供了与溶血栓剂,生长因子,血清白蛋白,血液因子或聚乙二醇缀合的多肽。