Related Experiment Videos
A chimeric streptokinase with unexpected fibrinolytic selectivity
J Goldstein1, G R Matsueda, S Y Shaw
1Macromolecular Structure, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08540, USA.
Thrombosis and Haemostasis
|September 1, 1996
Summary
A novel chimeric molecule, 59D8-streptokinase (SK), enhances fibrin targeting for improved clot lysis. This second-generation plasminogen activator shows unique activation properties and complete clot dissolution.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Streptokinase (SK) is a thrombolytic agent with limitations in specificity and efficacy.
- Fibrin-targeting strategies aim to improve the delivery and activity of plasminogen activators.
Purpose of the Study:
- To design and characterize a chimeric molecule, 59D8-SK, combining fibrin-targeting antibody 59D8 with streptokinase.
- To evaluate the fibrin-selectivity, activation kinetics, and clot lysis properties of 59D8-SK.
Main Methods:
- Fusion of the Fab fragment of 59D8 to streptokinase (SK).
- Expression and purification of chimeric 59D8-SK using affinity chromatography.
- Kinetic analysis of Glu-plasminogen activation and clot lysis assays in plasma and on clots.
Main Results:
- 59D8-SK demonstrated fibrin targeting, increasing plasma clot lysis by 2-fold.
- 59D8-SK exhibited a lag period in plasminogen activation, similar to wild-type SK, with comparable kinetic parameters.
- 59D8-SK showed reduced activity in plasma but was activated on clots, leading to slow but complete clot lysis, unlike the rapid but incomplete lysis by SK.
Conclusions:
- 59D8-SK represents a second-generation plasminogen activator with enhanced fibrin-selectivity and unique activation characteristics.
- The developed chimeric molecule offers potential for improved thrombolytic therapy due to its complete clot lysis capability.