A Kazal-type inhibitor of human mast cell tryptase: isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis
Research article published in Biol Chem Hoppe Seyler (1994)
Abstract
Human tryptase, a tetrameric proteinase expressed by mast cells, is virtually unique among the serine proteinases as it is not inhibited by any proteinaceous inhibitor tested so far. We have now isolated, sequenced, and characterized an inhibitor of human tryptase from the medical leech Hirudo medicinalis. LDTI (Leech-Derived Tryptase Inhibitor) was purified to apparent homogeneity by cation exchange and affinity chromatography. Amino acid sequencing of the protein consisting of 46 residues (M(r) 4738) revealed a high degree of similarity to the non-classical Kazal-type inhibitors bdellin B-3 and rhodniin, inhibitors isolated from the medical leech and the insect Rhodnius prolixus, respectively. LDTI is a tight-binding and relatively specific inhibitor of human tryptase; it inhibits only trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1) with similar affinities. Inhibition studies using small chromogenic substrates revealed that LDTI inhibits the amidolytic activity of tryptase by approximately 50%, suggesting that most likely due to steric hindrance LDTI binds to and inhibits only 2 of 4 active sites of tryptase. LDTI appears useful as a prototype of inhibitors of human tryptase and as a pharmacological tool for the investigation of the role of tryptase in health and disease.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Leech-Derived Tryptase Inhibitor (LDTI) isolated from Hirudo medicinalis; 46-residue Kazal-type inhibitor with high similarity to bdellin B-3 and rhodniin.
Por qué esto importa para la hirudoterapia
Este estudio describe el aislamiento, la purificación, la secuenciación de aminoácidos y la caracterización funcional del LDTI (inhibidor de triptasa derivado de sanguijuela, Leech-Derived Tryptase Inhibitor), una proteína de 46 residuos (Mr 4738) procedente de Hirudo medicinalis que inhibe la triptasa de mastocitos humanos —una serina proteinasa notablemente resistente a otros inhibidores proteicos conocidos. El LDTI muestra similitud con inhibidores no clásicos de tipo Kazal (bdellina B-3, rodniina) y también inhibe la tripsina y la quimotripsina con afinidad similar, uniéndose aproximadamente a dos de los cuatro sitios activos de la triptasa para reducir la actividad amidolítica en ~50%. Este trabajo es relevante para el dominio de ASH, ya que identifica y caracteriza un nuevo componente bioactivo del secretoma de la sanguijuela medicinal con potencial como herramienta farmacológica para estudiar la biología de la triptasa. La advertencia honesta es que se trata de un estudio de caracterización bioquímica sin datos in vivo, en animales ni clínicos; el resumen no formula afirmaciones terapéuticas ni de eficacia.
Citación
A Kazal-type inhibitor of human mast cell tryptase: isolation from the medical leech Hirudo medicinalis, characterization, and sequence analysis.
Sommerhoff CP et al. · Biol Chem Hoppe Seyler, 1994
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026