Protein analogues of tissue plasminogen activator

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase

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435212, 435219, 435 697, 530300, 530324, 530350, C12N 1500, C07K 14745, A61K 3849

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active

057006776

ABSTRACT:
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.

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