Parasite Metalo-aminopeptidases as Targets in Human Infectious Diseases.

Background: Parasitic human infectious diseases are a worldwide health problem due to the increased resistance to conventional drugs. For this reason, the identification of novel molecular targets and the discovery of new chemotherapeutic agents are urgently required. Metalo- aminopeptidases are promising targets in parasitic infections. They participate in crucial processes for parasite growth and pathogenesis.

Objective: In this review, we describe the structural, functional and kinetic properties, and inhibitors, of several parasite metalo-aminopeptidases, for their use as targets in parasitic diseases.

Conclusion: M1 and M17 aminopeptidases are essential enzymes for parasite development, and M18 aminopeptidase could be involved in hemoglobin digestion and erythrocyte invasion and egression. and acidic M17 aminopeptidases can play a nutritional role. T. brucei basic M17 aminopeptidase down-regulation delays the cytokinesis. The inhibition of Leishmania basic M17 aminopeptidase could affect parasite viability. methionyl aminopeptidase inhibition prevents apoptosis but not the parasite death. Decrease in M17 aminopeptidase activity produces cell wall structural modifications and encystation inhibition. Inhibition of growth is probably related to the inhibition of the parasite M17 aminopeptidase, probably involved in host hemoglobin degradation. M17 aminopeptidases inhibition may affect parasite development, since they could participate in hemoglobin degradation, surface membrane remodeling and eggs hatching. M17 aminopeptidase inhibition could attenuate parasite virulence, since it is apparently involved in the hydrolysis of cathepsin Cs- or proteasome-produced dipeptides and/or cell attachment/invasion processes. These data are relevant to validate these enzymes as targets.