Hirulog peptides with scissile bond replacements resistant to thrombin cleavage
Research article published in Biochemical and biophysical research communications (1991)
Abstract
Using the natural protein hirudin as a model, a novel class of synthetic peptide inhibitors were recently designed. These inhibitors, 'hirulogs', retain the carboxy terminal Hir53-64 domain that interacts with the anion binding exosite of thrombin, connected via an oligoglycyl spacer unit to a catalytic site-directed moiety modeled on the sequence [D]Phe-Pro-Arg-X. The scissile Arg-X bond bond of substrate-like inhibitors has been modified to the proteolytic-resistant functions as beta-homo amino acids Arg psi [CH2CONH] X (2) and reduced bond analogues Arg psi [CH2N]X (3). Both classes of compounds demonstrate inhibition of thrombin amidolytic activity, and this active-site inhibition is highly sensitive to the P1' residue X. Thus these hirulog derivatives are resistant to thrombin proteolysis while maintaining substrate-like interactions with the active center. Finally, hirulog derivatives with non-cleavable replacements of the scissile bond are found to be effective anticoagulant agents.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirulog peptides with scissile bond replacements resistant to thrombin cleavage.
Por qué esto importa para la hirudoterapia
Esta investigación estudió los 'hirulogs', una nueva clase de inhibidores peptídicos sintéticos modelados a partir de la hirudina natural de la sanguijuela, centrándose en modificaciones del enlace escindible que los hacen resistentes a la escisión por la trombina a la vez que mantienen la actividad anticoagulante. Esto resulta relevante para el ámbito de ASH porque traduce directamente el mecanismo estructural de un componente clave del secretoma de la sanguijuela (la hirudina) en principios viables de diseño farmacológico para nuevos anticoagulantes. Los hallazgos refuerzan la robustez terapéutica del mecanismo de doble unión de la hirudina. Sin embargo, una advertencia esencial es que este estudio se centra exclusivamente en miméticos sintetizados químicamente de péptidos de sanguijuela; no involucra sanguijuelas reales, secreciones naturales ni hirudoterapia con organismos completos.
Citación
Hirulog peptides with scissile bond replacements resistant to thrombin cleavage
Kline T et al. · Biochemical and biophysical research communications, 1991
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026