Design of a thrombin inhibitory staphylokinase based plasminogen activator with anti-reocclusion potential.

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.

Cloning and purification of an anti-thrombotic, chimeric Staphylokinase in Pichia pastoris.

There has been an increasing prevalence of cardiovascular diseases such as myocardial infarction and stroke in modern societies because of multiple lifestyle related issues like sedentariness and obesity, alcohol consumption and many more "life-style"factors. The FDA-approved thrombolytics such as Tissue Plasminogen Activator, Streptokinase etc. are used to lyse the clots in thrombotic disorders such as myocardial infarction, stroke etc.

Formation of Se(0), Te(0), and Se(0)-Te(0) nanostructures during simultaneous bioreduction of selenite and tellurite in a UASB reactor.

Simultaneous removal of selenite and tellurite from synthetic wastewater was achieved through microbial reduction in a lab-scale upflow anaerobic sludge blanket reactor operated with 12 h hydraulic retention time at 30 °C and pH 7 for 120 days. Lactate was supplied as electron donor at an organic loading rate of 528 or 880 mg COD L day. The reactor was initially fed with a synthetic influent containing 0.

Continuous removal and recovery of tellurium in an upflow anaerobic granular sludge bed reactor.

Continuous removal of tellurite (TeO) from synthetic wastewater and subsequent recovery in the form of elemental tellurium was studied in an upflow anaerobic granular sludge bed (UASB) reactor operated at 30°C. The UASB reactor was inoculated with anaerobic granular sludge and fed with lactate as carbon source and electron donor at an organic loading rate of 0.6g CODLd.

Amino-Terminal Fusion of Epidermal Growth Factor 4,5,6 Domains of Human Thrombomodulin on Streptokinase Confers Anti-Reocclusion Characteristics along with Plasmin-Mediated Clot Specificity.

Streptokinase (SK) is a potent clot dissolver but lacks fibrin clot specificity as it activates human plasminogen (HPG) into human plasmin (HPN) throughout the system leading to increased risk of bleeding. Another major drawback associated with all thrombolytics, including tissue plasminogen activator, is the generation of transient thrombin and release of clot-bound thrombin that promotes reformation of clots. In order to obtain anti-thrombotic as well as clot-specificity properties in SK, cDNAs encoding the EGF 4,5,6 domains of human thrombomodulin were fused with that of streptokinase, either at its N- or C-termini, and expressed these in Pichia pastoris followed by purification and structural-functional characterization, including plasminogen activation, thrombin inhibition, and Protein C activation characteristics.

Site-Specific Thiol-mediated PEGylation of Streptokinase Leads to Improved Properties with Clinical Potential.

Streptokinase (SK) is an efficient thrombolytic agent that dissolves fibrin blood clots with clinical efficiency comparable to the high priced drug, tissue plasminogen activator (tPA). However, being of bacterial origin, its major drawbacks are its potentially high antigenicity, and relatively short circulating half-life (approximately 10-15 min). In the present investigation, an attempt has been made to address both these shortcomings by site-specific pegylation, and to obtain longer lasting thrombolytics, which are consistent with clinical requirements.