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

Resumen

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, synthe-
sis, and turnover of proteins and regulate most biochemical and physiologi-
cal 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 in-
fectious 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 distrib-
uted 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 de-
velopment of therapeutic agents for human diseases including cancer, hy-
pertension, central nervous system disorders, inflammation, immune sys-
tem disorders, skin pathologies and infectious diseases, like malaria and
coronavirus-induced syndromes. The relevance of exopeptidases has driv-
en 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.