Anti-malaria drug development targeting the M1 alanyl and M17 leucyl aminopeptidases

The M1 alanyl aminopeptidase and M17 leucyl aminopeptidase are critical to the growth and development of malaria parasites inside host erythrocytes. Potent aminopeptidase inhibitors kill malaria parasites in culture and are also active in vivo against murine malaria. Functional recombinant enzyme studies have been used to decipher the three-dimensional structures of both enzymes that together with new and specific inhibitors are facilitating structure-activity-relationship (SAR) and functional studies. Here we review the progress made in our knowledge of these two enzymes which is bringing them closer to being validated anti-malarial drug targets.