Pro-urokinase mutants

Details Pro-urokinase mutants Pro-urokinase mutants

1993-07-02

1995-12-05

Wax, Robert A.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

435212, 435215, C12N 972, C12N 948, A61K 3849

Patent

active

054726921

ABSTRACT:
The invention relates to thrombolytically active pro-urokinase (pro-UK) mutants comprising the amino acid sequence of native pro-UK, but including a mutation which causes the pro-UK mutants to induce less fibrinogenolysis and non-specific plasminogen activation than native pro-UK, to have at least a 10-fold lower intrinsic activity than native pro-UK, and to have substantially the same fibrin promotion and thrombolytic activity after plasmin activation compared to native pro-UK when administered to a patient.

REFERENCES:
patent: 5108901 (1992-04-01), Anderson
Harris, T. J. R. "Second-Generation Plasminogen Activators," Protein Engineering 1(6):449-458 (1987).
Brooks et al., J. Comp. Chem., 4:187-217 (1983).
Heckel et al., J. Comp. Aided Mol. Des., 2:7-14 (1988).
Liu et al., Biochemistry, 31:6311-6317 (1992).
Nienaber et al., Biochemistry, 31:3852-3861 (1992).
Peterson et al., Biochem., 29:3451-57 (1990).
Wang et al. J. Mol. Biol., 185:595-624 (1985).

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