TPA MODIFIED IN THE GROWTH FACTOR DOMAIN AND 1ST AND 2ND KRINGLE REGIONS; AND PROCESS FOR PREPARATION THEREOF

摘要

A novel tissue plasminogen activator (tPA) derivative has an amino acid sequence which corresponds to that of naturally occurring tPA but in which the amino acids of the naturally occurring tPA molecule which form the EGF domain are absent and at least one of the kringels I or II, the connecting region, the catalytic region and the fibrin finger are present; in particular, the subsequent amino acids up to at least the first disulphide bridge of the domain of kringel I or all amino acids of the domain of kringel I up to the first disulphide bridge of the domain of kringel II or kringel II may additionally be absent. The novel derivative can be prepared, for example, by cleaving the section which encodes the amino acid sequence which is absent in the derivative in comparison with the complete tPA molecule out of the tPA-cDNA using the corresponding restriction endonucleases, linking the sections which encode the desired tPA derivative, incorporating the resulting tPA-derivative-cDNA into a prokaryotes using a suitable vector, and expressing it therein. The novel derivative has the characteristic biological properties of tPA but its half-life is improved.