A novel stearic acid-modified hirudin peptidomimetic with improved pharmacokinetic properties and anticoagulant activity
Drug discovery study published in Scientific Reports (2015)
Abstract
A novel hirudin isoform 3 mimetic peptide, named peptide S2, has been prepared by introduction of a stearic acid modification. Peptide S2 exhibited superior inhibitory activity to hirulog-1 (Bivariludin) and showed significantly higher anticoagulant potency in vivo. Peptide S2 elevated the thrombin time, prothrombin time and activated partial thromboplastin time of rat and human plasma more efficiently than hirulog-1 and the unmodified form of peptide S2 (peptide 1). Furthermore, peptide S2 inhibited arterial thrombosis and inferior vena cava in rat model 8 h after administration, and was 10-fold more potent than hirulog-1 300 min after administration of 0.1 μmol/kg peptide. The enhanced antithrombotic activity could be attributed to its long half-life (T1/2 = 212.2 ± 58.4 min), which was 13.1 and 14.7-fold longer than those of hirulog-1 (T1/2 = 15.1 ± 1.3 min) and peptide 1 (T1/2 = 13.5 ± 2.6 min), respectively. Further enzymatic degradation and binding assay with human serum albumin (HSA) demonstrated that the longer duration time should be originated from the slowing of trypsin or thrombin-mediated degradation, as well as its binding to HSA. The improved pharmacokinetic properties observed for peptide S2 has made it a promising therapeutic agent for the treatment of thrombi-related diseases.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Stearic acid-modified hirudin isoform 3 mimetic peptide (peptide S2) showed 13.1-fold longer half-life than hirulog-1 (T1/2 212.2 vs 15.1 min) and 10-fold improved antithrombotic potency, attributed to slowed proteolysis and HSA binding.
Por qué esto importa para la hirudoterapia
Este estudio describe un péptido mimético de la isoforma 3 de hirudina modificado con ácido esteárico (péptido S2) diseñado para mejorar las propiedades farmacocinéticas y la actividad anticoagulante. El péptido S2 mostró una inhibición superior de la trombina y una potencia anticoagulante mayor en comparación con hirulog-1 (bivalirudina) en plasma de rata y humano, con una vida media de 212,2 ± 58,4 minutos —aproximadamente 13–15 veces superior a la de hirulog-1 y la del péptido no modificado— e inhibió la trombosis arterial y de la vena cava inferior en modelos de rata. Este trabajo es relevante, ya que representa la ingeniería racional de una molécula basada en hirudina para una acción antitrombótica sostenida. Sin embargo, los datos son completamente preclínicos, procedentes de modelos en rata y ensayos in vitro; el péptido S2 es un peptidomimético sintético, no un producto natural de secreción de la sanguijuela, y no se informan estudios en humanos.
Citación
A novel stearic acid-modified hirudin peptidomimetic with improved pharmacokinetic properties and anticoagulant activity.
Liu Z et al. · Scientific Reports, 2015
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026