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Thromb Haemost 1993; 70(02): 326-331
DOI: 10.1055/s-0038-1649574
Original Articles
Fibrinolysis
Schattauer GmbH Stuttgart

Functional Properties of p-Anisoylated Plasmin-Staphylokinase Complex

H R Lijnen
The Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
B Van Hoef
The Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
,
R A G Smith
1   SmithKline Beecham Pharmaceuticals, Biosciences Research center, Epsom, UK
,
D Collen
The Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Received 20 December 1992

Accepted after revision 11 February 1993

Publication Date:
04 July 2018 (online)

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Summary

The kinetic and fibrinolytic properties of a reversibly acylated stoichiometric complex between human plasmin and recombinant staphylokinase (plasmin-STAR complex) were evaluated. The acylation rate constant of plasmin-STAR by p-amidinophenyl-p’-anisate-HCI was 52 M-1 s-1 and its deacylation rate constant 1.2 × 10-4 s-1 (t½ of 95 min) which are respectively 50-fold and around 3-fold lower than for the plasmin-streptokinase complex. The acylated complex was stable as evidenced by binding to lysine-Sepharose. However, following an initial short lag phase, the acylated plasmin-STAR complex activated plasminogen at a similar rate as the unblocked complex, whereas the acylated plasmin-streptokinase complex did not activate plasminogen. These findings indicate that STAR, unlike streptokinase, dissociates from its acylated complex with plasmin in the presence of excess plasminogen. In agreement with this hypothesis, the time course of the lysis of a 125I-fibrin labeled plasma clot submerged in citrated human plasma, is similar for acylated plasmin-STAR, unblocked plasmin-STAR and free STAR (50% clot lysis in 2 h requires 12 nM of each agent). The plasma clearances of STAR-related antigen following bolus injection in hamsters were 1.0 to 1.5 ml/min for acylated plasmin-STAR, unblocked plasmin-STAR and free STAR, as a result of short initial half-lives of 2.0 to 2.5 min.

The dissociation of the anisoylated plasmin-STAR complex and its consequent rapid clearance suggest that it has no apparent advantages as compared to free STAR for clinical thrombolysis.

 

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