A novel hirudin derivative characterized with anti-platelet aggregations and thrombin inhibition
Research article published in Journal of thrombosis and thrombolysis (2008)
Abstract
BACKGROUND: Hirudin is an anti-coagulative product of the salivary glands of the medicinal leech Hirudo medicinalis. It is a powerful and specific thrombin inhibitor. Peptides containing the RGD motif competitively inhibit the binding of fibrinogen to GP IIb/IIIa on the platelets, thus inhibiting platelet aggregation. RESULTS: We have constructed a recombinant RGD-hirudin (r-RGD-hirudin) by fusing the tripeptide RGD sequence to the native hirudin (wt-hirudin). The r-RGD-hirudin was expressed at high levels in Pichia pastoris, and was purified to approximately 97% homogeneity. The specific anti-thrombin activity of purified r-RGD-hirudin is 12,000 ATU/mg, which is equivalent to wt-hirudin, but only r-RGD-hirudin can inhibit platelet aggregation. The biological effects of r-RGD-hirudin on Thrombin Time (TT), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), Bleeding Time (BT), maximum platelet aggregation (PAGm) induced by ADP were studied in rabbit model and compared with that of wt-hirudin. The rabbits were infused r-RGD-hirudin had prolonged TT, PT, and aPTT which were similar to that of wt-hirudin; but only r-RGD-hirudin was capable of inhibiting PAGm. Histopathological analyses showed that r-RGD-hirudin was two to three times more effective than wt-hirudin in preventing thrombosis. CONCLUSIONS: r-RGD-hirudin can potentially be used as a novel anti-coagulant for the prevention of thrombosis after carotid artery anastomosis or in other thrombotic events.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin is an anti-coagulative product of the salivary glands of the medicinal leech Hirudo medicinalis.
Por qué esto importa para la hirudoterapia
Este estudio construyó una RGD-hirudina recombinante mediante la fusión de un tripéptido RGD a la hirudina nativa de Hirudo medicinalis, la expresó en Pichia pastoris y evaluó sus actividades anticoagulante y antiplaquetaria duales en conejos. La r-RGD-hirudina mantuvo una actividad antitrombina equivalente (12.000 ATU/mg) a la de la hirudina de tipo silvestre, al mismo tiempo que inhibió de forma exclusiva la agregación plaquetaria inducida por ADP, y fue de dos a tres veces más eficaz en la prevención de la trombosis histopatológicamente. Esto es relevante para el ámbito de la ASH, ya que diseña un derivado bifuncional mejorado de un anticoagulante derivado de sanguijuela. Sin embargo, se trata de un estudio preclínico en animales sin sanguijuelas ni hirudoterapia involucradas; la molécula es un constructo de fusión recombinante en lugar de un componente natural de la secreción de la sanguijuela.
Citación
A novel hirudin derivative characterized with anti-platelet aggregations and thrombin inhibition
Mo W et al. · Journal of thrombosis and thrombolysis, 2008
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026