abstract |
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. |