A mutant streptokinase lacking the C-terminal 42 amino acids is less immunogenic

Torréns, Isis; Ojalvo, Ariana G.; Seralena, Alina; Hayes, Orlando; Fuente, José de la

doi:10.1016/s0165-2478(99)00151-0

Cited by 25 publications

(14 citation statements)

References 21 publications

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“…Recombinant strepto kinases with reduced immunogenicity have been produced. A mutant streptokinase that lacks the C terminal 42 amino acids was found to be less immunogenic than the native molecule 6 . One chemical modification has involved complexing streptokinase with PEG [7][8][9] , primarily for reducing immunogenecity.…”

Section: Fig1: Schematic Representation Of Fibrinolysismentioning

confidence: 97%

Untitled

2013

IJPSR

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A novel fibrinolytic protease from Bacillus circulans GD25 was isolated and characterized for the fibrinolytic activity. The fibrinolytic protease was purified by ammonium sulphate fractionation (70%) and subjected to chromatographic methods like Sephadex G-50, DEAE-Sephadex A-50 columns. The purified enzyme has an approximately 38 kDa in size by SDS-PAGE and gel filtration. Optimum activity was at 35ºC and the enzyme was highly active over a wide range of pH from 7.0-9.0 with an optimum at pH 8.0. It exhibited stronger fibrinolytic protease activity. The activity was slightly enhanced by Ca 2+ and Mg 2+ whereas Zn 2+, Cu 2+, Co 2+ and Fe 2+ suppressed the activity. The fibrinolytic protease activity was totally lost in the presence of PMSF, suggesting that the purified enzyme is a serine metallo-protease with potential application in thrombolytic therapy INTRODUCTION: Proteases are proteolytic enzymes which catalyze the hydrolysis of proteins based upon their structures or properties of the active site. There are several kinds of proteases such as serine, metallo, carboxyl, acidic, neutral and alkaline proteases. Proteases are industrially important due to their wide applications in leather processing, detergent industry, food industries, pharmaceutical and textile industry etc 1, 2. Proteases are obtained from plants, animal organs and microorganisms, with the majority obtained from microbial sources. Currently, a large proportion of commercially available proteases are derived from bacteria and fungi.

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Section: Fig1: Schematic Representation Of Fibrinolysismentioning

confidence: 97%

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2013

IJPSR

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“…The deletion of 42 residues of streptokinase from C-terminus has been shown to reduce its immunogenicity. 37 The pathogenic nature of the natural isolate led coworkers to subclone the gene in several heterologous expression platforms. Extensive work has been carried out on recombinant streptokinase expression in the E. coli host with upto 25,000 IU/mL of the recombinant protein.…”

Section: First Generation Plasminogen Activatorsmentioning

confidence: 99%

The evolution of recombinant thrombolytics: Current status and future directions

Adivitiya

Khasa

2016

Bioengineered

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Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

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“…Another chemical modification involved complexing SK with PEG, primarily for reducing immunogenicity. 143 SK variants with one or more of the normal amino acids residues replaced by others have been prepared in attempts to enhance plasminogen activation. Some of the modified variants displayed an enhanced stability.…”

Section: Streptokinasementioning

confidence: 99%

“…A mutant SK that lacked the C‐terminal 42 amino acids was found to be less immunogenic. Another chemical modification involved complexing SK with PEG, primarily for reducing immunogenicity …”

Section: Introductionmentioning

confidence: 99%

The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi

Kotb

2014

Biotechnology Progress

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Formation of endogenous thrombi in blood vessels is one of the leading causes of death in our modern life. According to data provided by the World Health Organization (WHO) in 2000, heart diseases are responsible for 29% of the total mortality rate in the world. For this, a tremendous amount of research has been done in the area of prevention and treatment of these diseases. The classical therapy of these thrombi relies upon the use of antiplatelets, anticoagulants, or even surgeries. Relatively recently, the fibrinolytic enzymes produced by microorganisms, snakes, earthworms, insects, plants, and other organisms are being successfully used in the treatment of blood clots, especially with regard to the direct dissolving action on fibrin in tandem with less cost and side effects in comparison with the first-generation thrombolytic agents, streptokinase and urokinase. Furthermore, recombinant DNA technology has succeeded in improving and decreasing the undesirable effects of the first generation of enzymes. Recombinant PAs or rt-PAs like alteplase, retelase, saruplase, tenecteplase, lanoteplase, and desmoteplase became available in the drug markets with advantages of less binding loci with PAI-1 to avoid degradation while providing faster and more complete reperfusion in a greater number of patients with less risk of bleeding and intracranial hemorrhage. This review is the first to cover all the natural and recombinant thrombolytic agents used in enzyme therapy.

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A mutant streptokinase lacking the C-terminal 42 amino acids is less immunogenic

Cited by 25 publications

References 21 publications

Untitled

Untitled

The evolution of recombinant thrombolytics: Current status and future directions

The biotechnological potential of fibrinolytic enzymes in the dissolution of endogenous blood thrombi

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