Streptokinase-plasminogen complex

An exogenous plasminogen activator that has been used in clinical trials as a fibrinolytic agent is the 53-kDa single-chain polypeptide called streptokinase (SK). It forms a complex with plasminogen on an equimolar basis. The resulting 156-kDa streptokinase-plasminogen complex (plg-SK) converts Glu-plasmino-gen to Glu-plasmin (41). 

Streptokinase induces its thrombolytic effect by binding specifically and tightly to plasminogen. This induces a conformational change in the plasminogen molecule that renders it proteolytically active. In this way, the streptokinase-plasminogen complex catalyses the proteolytic conversion of plasminogen to active plasmin. 

Anistreplase (streptokinase- plasminogen complex) streptococci protein streptococci plaminogen, which is then cleaved to form plasmin. Plasmin mediate fibrinolysis. Systemic lytic state and immunogenicity may limit its use. Because antistreplase is aheadly lined to plaminogen, the onset of fibrinolytic is faster. These enzymes are not fibrin-specific. 

Preparation of freeze dried p-anisoyl streptokinase/plasminogen complex without internal peptide bond cleavages ... 

O. Matsuo, D. Collen, and M. Verstrate. On the fibrinolytic and thrombolytic properties of active site p-anisoylated streptokinase-plasminogen-complex (BRL 26921). Thromb. Res. 24 347 (1981). 

Wang, S., G.L Reed, L. Hedstrom, Zymogen activation in the streptokinase-plasminogen complex. Ilel is required for the formation of a functional active site. Eur J Biochem 2000, 267, 3994-4001. 

Fig. 4. Fibrinolytic system where SCUPA is single-chain urokinase plasminogen activator rTPA is recombinant tissue plasminogen activator APSAC is acylated plasminogen streptokinase activator complex SK is streptokinase and UK is urokinase.

APSAC = acylated plasminogen streptokinase activator complex. 

Acyclo-retinoic acid, 17 662 Acylaminoanthraquinone dyes, 9 333, 334 Acylated plasminogen-streptokinase activator complex, 5 175, 177-178 Acylates, titanium, 25 96 Acylating agents, 12 174 Acylation, 9 282 12 173-188... 

Streptokinase is a protein (but not an enzyme in itself) synthesized by streptococci that combines with the proactivator plasminogen. This enzymatic complex catalyzes the conversion of inactive plasminogen to active plasmin. Urokinase is a human enzyme synthesized by the kidney that directly converts plasminogen to active plasmin. Plasmin itself cannot be used because naturally occurring inhibitors in plasma prevent its effects. However, the absence of inhibitors for urokinase and the streptokinase-proactivator complex permits their use clinically. Plasmin formed inside a thrombus by these activators is protected from plasma antiplasmins, which allows it to lyse the thrombus from within. 

Anistreplase (anisoylated plasminogen streptokinase activator complex APSAC) consists of a complex of purified human plasminogen and bacterial streptokinase that has been acylated to protect the enzyme s active site. When administered, the acyl group spontaneously hydrolyzes, freeing the activated streptokinase-proactivator complex. This product (recently discontinued in the USA) allows for rapid intravenous injection, greater clot selectivity (ie, more activity on plasminogen associated with clots than on free plasminogen in the blood), and more thrombolytic activity. 

Common Name Eminase Fibrit Iminase Multilase Anisoylated plasminogen streptokinase activator complex... 

J, L, Anderaon, J. B. Boissel, and D. A. Chamberlain, eds. Symposium on nnisoylnted plasminogen streptokinase activator complex (AFSAQ, Drugs3-33 (1987)-... 

In addition to the described preparation, for continuous infusion of a thrombolytic test solution a polyethylene catheter is inserted in the jugular vein. One and a half hours after implantation of the wire coil, the test compound or the vehicle (controls) is infused for up to 2.5 h. The wire coil is then removed and the protein content of thrombi is determined (see above). Bernat et al. (1986) demonstrated the fibrinolytic activity of urokinase and streptokinase-human plasminogen complex in this model. 

Anistreplase (anisoylated plasminogen streptokinase activator complex, APSAC), is the plasminogen-streptokinase complex (above) in which the enzyme centre that converts plasminogen to plasmin is protected from deactivation, so prolonging its action. 

Been M, de Bono DP, Muir AL, Boulton FE, Fears R, Standring R, Ferres H. Clinical effects and kinetic properties of intravenous APSAC—anisoylated plasminogen-streptokinase activator complex (BRL 26921) in acute myocardial infarction. Int J Cardiol 1986 11(1) 53-61. 

Bucknall C, Darley C, Flax J, Vincent R, Chamberlain D. Vasculitis complicating treatment with intravenous anisoy-lated plasminogen streptokinase activator complex in acute myocardial infarction. Br Heart J 1988 59(1) 9-11. 

Plasmin-streptokinase-activator complex Plasminogen activation Thrombolysis 23-25... 

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