Novel cysteine protease inhibitor derived from the leech: recombinant expression, purification, and characterization
Recombinant expression published in Toxins (2021)
Abstract
Cathepsin L (CatL) is a lysosomal cysteine protease primarily involved in the terminal degradation of intracellular and endocytosed proteins. More specifically, in humans, CatL has been implicated in cancer progression and metastasis, as well as coronary artery diseases and others. Given this, the search for potent CatL inhibitors is of great importance. In the search for new molecules to perform proteolytic activity regulation, salivary secretions from hematophagous animals have been an important source, as they present protease inhibitors that evolved to disable host proteases. Based on the transcriptome of the Haementeria vizzotoi leech, the cDNA of Cystatin-Hv was selected for this study. Cystatin-Hv was expressed in Pichia pastoris and purified by two chromatographic steps. The kinetic results using human CatL indicated that Cystatin-Hv, in its recombinant form, is a potent inhibitor of this protease, with a Ki value of 7.9 nM. Consequently, the present study describes, for the first time, the attainment and the biochemical characterization of a recombinant cystatin from leeches as a potent CatL inhibitor. While searching out for new molecules of therapeutic interest, this leech cystatin opens up possibilities for the future use of this molecule in studies involving cellular and in vivo models.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Recombinant expression and characterization of a novel cysteine protease inhibitor from leech — expanding the leech-derived protease-inhibitor catalog.
Por qué esto importa para la hirudoterapia
Este estudio identificó, expresó en Pichia pastoris y caracterizó bioquímicamente Cystatin-Hv, un inhibidor recombinante de cisteín-proteasas procedente del transcriptoma de la sanguijuela Haementeria vizzotoi, demostrando una inhibición potente de la catepsina L humana (Ki = 7,9 nM). Dada la implicación de la catepsina L en la progresión del cáncer, la metástasis y la enfermedad arterial coronaria, este hallazgo es relevante para el ámbito de ASH como descubrimiento de una nueva molécula bioactiva derivada de la sanguijuela. No obstante, el trabajo es puramente bioquímico (expresión recombinante y ensayo cinético), sin datos celulares ni in vivo, y sin conexión directa con la práctica de la hirudoterapia. El potencial terapéutico es prospectivo y no está validado más allá de la inhibición a nivel enzimático.
Citación
Novel cysteine protease inhibitor derived from the leech: recombinant expression, purification, and characterization.
Linhares DDC et al. · Toxins, 2021
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026