Marine organisms : a source of biomedically relevant metallo M1, M2 and M17 exopeptidase inhibitors

Los organismos marinos: Fuente de inhibidores de exopeptidasas de tipo metalo M1, M2 y M17 de relevancia biomédica

Isel Pascual Alonso , Laura Rivera Méndez , Fabiola Almeida , Mario Ernesto Valdés Tresano , Yarini Arrebola Sánchez , Aida Hernández-Zanuy , Luis Álvarez-Lajonchere , Dagmara Díaz , Belinda Sánchez , Isabelle Florent (1) , Marjorie Schmitt (2) , Miguel Cisneros , Jean Louis Charli

1 MCAM - Molécules de Communication et Adaptation des Micro-organismes
2 LIMA - Laboratoire d'innovation moléculaire et applications

Proteolytic enzymes, known as peptidases or proteases, are critical in all living organisms. They can act as exo-and/or endo-peptidases. Peptidases are segregated in classes that strongly depend on the chemical nature of the groups involved in catalysis. Peptidases control the activation, synthesis , and turnover of proteins and regulate most biochemical and physiological processes. They are consequently major regulators of homeostasis, ageing, diseases, and death. Proteases are also essential for propagation of infectious agents, being major contributors of pathogenesis in several infectious diseases, including the current coronavirus emergent pandemic COVID-19. Exopeptidases catalyze the cleavage of the N-terminal or C-terminal amino acids of proteins or peptide substrates. They are distributed in many phylla and play critical roles in physiology and pathophysiolo-gy. Most of them are metallo peptidases belonging to the M1, M2, and M17 families, among others. Some, such as M1 aminopeptidases N, A and thyrotropin-releasing hormone degrading ectoenzyme, M2 angiotensin converting enzyme and M17 leucyl aminopeptidase are targets for the development of therapeutic agents for human diseases including cancer, hy-pertension, central nervous system disorders, inflammation, immune system disorders, skin pathologies and infectious diseases, like malaria and coronavirus-induced syndromes. The relevance of exopeptidases has driven the search and identification of potent and selective inhibitors, as major tools to control proteolysis with impact in biochemistry, biotechnology, and biomedicine. The present contribution focuses on marine biodiversity as an important and promising source of inhibitors of metallo exopeptidas-es from different families, with biomedical applications in human diseases.

Keywords: exopeptidases; aminopeptidase N; aminopeptidase A; TRH -degrading ectoenzyme; angiotensin converting enzyme; leucyl aminopeptidase; inhibitors; marine organisms

Domains: Life Sciences [q-bio]; Chemical Sciences

Isel Pascual Alonso, Laura Rivera Méndez, Fabiola Almeida, Mario Ernesto Valdés Tresano, Yarini Arrebola Sánchez, et al.. Marine organisms : a source of biomedically relevant metallo M1, M2 and M17 exopeptidase inhibitors. REVISTA CUBANA DE CIENCIAS BIOLÓGICAS, 2020, 8 (2), pp.1-36. ⟨hal-02944434⟩