Production and characterization of saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion to collagen
Biochemistry article published in Seminars in Thrombosis and Hemostasis (2001)
Abstract
Platelets tether to collagen in both a von Willebrand factor (vWF)-dependent and a vWF-independent manner. We have recently characterized a recombinant protein, saratin, isolated from the saliva of the leech Hirudo medicinalis, expressed it in Hansenula polymorpha, and studied its effect on direct and indirect platelet-collagen interactions. Saratin dose dependently inhibited the binding of purified human vWF to human type I and III collagens (IC(50)= 0.23 +/- 0.004 and 0.81 +/- 0.04 microg mL(-1), respectively) and to calf skin collagen (IC(50)= 0.44 +/- 0.008 microg mL(-1)). Furthermore, saratin showed a similar inhibitory potency against the binding of human, rodent, and porcine plasma vWF to these collagens. In a flow chamber under conditions of elevated shear (2700 s(-1)), saratin dose dependently and potently inhibited platelet aggregate formation on a collagen-coated surface (IC(50)= 0.96 +/- 0.25 microg mL(-1)), but at reduced shear (1300 s(-1)) a rightward shift in the dose-response curve was noted (IC(50)= 5.2 +/- 1.4 microg mL(-1)). Surface plasmon resonance analysis revealed both high and low affinity binding sites for saratin on human collagen type III (K(d) 5 x 10(-8) M and 2 x 10(-6) M, respectively). Although low concentrations of saratin, which inhibited platelet adhesion under increased shear (i.e., saturation of high-affinity binding sites), had no effect on vWF-independent collagen-induced platelet aggregation, high concentrations (i.e., saturation of low-affinity binding sites) were found to inhibit platelet aggregation. These data demonstrate that saratin is a potent inhibitor of vWF-dependent platelet adhesion to collagen and hence may have therapeutic potential as an antithrombotic agent.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Production of recombinant saratin from Hansenula polymorpha and characterization showing dose-dependent inhibition of vWF binding to types I/III collagen and shear-dependent inhibition of platelet aggregate formation.
Por qué esto importa para la hirudoterapia
Este trabajo caracterizó la saratina recombinante, una proteína de la secreción salival de Hirudo medicinalis expresada en Hansenula polymorpha, examinando su inhibición de las interacciones plaqueta-colágeno dependientes e independientes del factor de von Willebrand (vWF). La saratina bloqueó de forma dosis-dependiente la unión del vWF humano purificado y del vWF plasmático a los colágenos tipo I/III, e inhibió potentemente la formación de agregados plaquetarios sobre el colágeno bajo cizallamiento elevado, con análisis de resonancia de plasmón superficial que revelaron sitios de unión al colágeno de alta y baja afinidad. Para el dominio de la ASH, esto es directamente relevante porque describe una molécula definida del secretoma de la sanguijuela con actividad antitrombótica mecanística en la interfaz plaqueta-colágeno. Advertencia: los datos son hallazgos bioquímicos y de cámara de flujo in vitro (utilizando plasma humano, de roedor y porcino), no resultados clínicos, y la afirmación del resumen sobre potencial terapéutico es inferencial más que demostrada en pacientes.
Citación
Production and characterization of saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion to collagen.
Barnes CS, Krafft B, Frech M et al. · Seminars in thrombosis and hemostasis, 2001
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 26, 2026 · Última actualización del sitio: 18 de junio de 2026