Arora, Kashika and Maheshwari, Neeraj and Sahni, Girish (2020) Design of a thrombin inhibitory staphylokinase based plasminogen activator with anti-reocclusion potential. International journal of biological macromolecules, 144. pp. 791-800. ISSN 1879-0003
Full text not available from this repository. (Request a copy)Abstract
In the quest of a therapeutically improved thrombolytic drug, we designed and expressed a Staphylokinase based, recombinant fusion protein with fibrin specific clot lysis and anti-thrombin activities derived from human thrombomodulin, a transmembrane glycoprotein with anticoagulant properties, known to form a complex with thrombin and then activating Protein C. The fusion construct was expressed in the yeast Pichia pastoris for cost effective and facile production. The purified construct had comparable plasminogen activation and clot lysis capability as compared to native SAK in that it showed plasmin dependent Plasminogen activation, but exhibited significantly lower fibrinogenolysis (an indicator of fibrin-specific action) even at much higher doses than SAK. In addition, its successful activation of the thrombin-mediated Protein C anticoagulant pathway was reflected in increased in vitro plasma clotting time, as well as inhibition of clot bound thrombin, which led to nearly 15-25% lesser re-formation of fibrin clots after initial successful clot lysis in a specially designed in vitro assay for re-occlusion. Thus, this novel chimeric protein could be of high therapeutic potential as a thrombolytic drug with enhanced fibrin specific clot dissolving properties along with lower bleeding and re-thrombosis complications- a dire need today, especially in the treatment of thrombotic strokes.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to Elsevier Science. |
| Uncontrolled Keywords: | Pichia pastoris; Staphylokinase; Thrombomodulin |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 26 Feb 2020 15:04 |
| Last Modified: | 26 Feb 2020 15:04 |
| URI: | http://crdd.osdd.net/open/id/eprint/2544 |
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