Evaluation of a multifunctional staphylokinase variant with thrombin inhibition and antiplatelet aggregation activities produced from salt-inducible E. coli GJ1158
Translational study published in Canadian Journal of Physiology and Pharmacology (2013)
Abstract
Reocclusion is one of the major root causes for secondary complications that arise during thrombolytic therapy. A multifunctional staphylokinase variant SRH (staphylokinase (SAK) linked with tripeptide RGD and didecapeptide Hirulog) with antiplatelet and antithrombin activities in addition to clot specific thrombolytic function, was developed to address the reocclusion problem. We preferred to use Escherichia coli GJ1158 as the host in this study for economic production of SRH by osmotic (0.3 mol/L sodium chloride) induction, to overcome the problems associated with the yeast expression system. The therapeutic potential of SRH was evaluated in the murine model of vascular thrombosis. The SAK protein (1 mg/kg body mass) and SRH protein (1 mg/kg and 2 mg/kg) were administered intravenously to the different treatment groups. The results have shown a dose-dependent antithrombotic effect in carrageenan-induced mouse tail thrombosis. The thrombin time, activated partial thromboplastin time, and prothrombin time were significantly prolonged (p < 0.05) in the SRH-infused groups. Moreover, SRH inhibited platelet aggregation in a dose-dependent manner (p < 0.05), while the bleeding time was significantly (p < 0.05) prolonged. All of these results inferred that the osmotically produced multifunctional fusion protein SRH (SAK-RGD-Hirulog) is a promising thrombolytic agent, and one which sustained its multifunctionality in the animal models.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Multifunctional SRH fusion (staphylokinase-RGD-hirulog) had antithrombin, antiplatelet, and clot-specific thrombolytic activity in a murine carrageenan vascular thrombosis model and significantly prolonged aPTT/PT/TT/bleeding time.
Por qué esto importa para la hirudoterapia
Este estudio desarrolló una proteína de fusión multifuncional SRH (estafiloquinasa vinculada con el tripéptido RGD y el didecapéptido Hirulog) producida mediante expresión inducible por sal en E. coli GJ1158, combinando actividades trombolítica, antitrombínica y antiplaquetaria para abordar la reoclusión durante la terapia trombolítica. En un modelo de trombosis de cola de ratón inducida por carragenina, SRH mostró efectos antitrombóticos dependientes de la dosis, prolongó significativamente el tiempo de trombina, el aPTT y el tiempo de protrombina (P<0.05), e inhibió la agregación plaquetaria, aunque el tiempo de sangrado también se prolongó significativamente. El componente Hirulog proporciona un vínculo directo con la familia de inhibidores de trombina de la hirudina. Sin embargo, se trata de un estudio preclínico en animales de una proteína de fusión recombinante diseñada; no es un estudio de terapia con sanguijuelas ni del secretoma de la sanguijuela, y el elemento derivado de la hirudina es un dominio funcional dentro de un constructo multicomponente.
Citación
Evaluation of a multifunctional staphylokinase variant with thrombin inhibition and antiplatelet aggregation activities produced from salt-inducible E. coli GJ1158.
Kumar A et al. · Canadian Journal of Physiology and Pharmacology, 2013
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026