Metalloaminopeptidases of the Protozoan Parasite Plasmodium falciparum as Targets for the Discovery of Novel Antimalarial Drugs

Malaria poses a significant threat to approximately half of the world’s population with an annual death toll close to half a million. The emergence of resistance to front-line antimalarials in the most lethal human parasite species, Plasmodium falciparum (Pf), threatens progress made in malaria control. The prospect of losing the efficacy of antimalarial drugs is driving the search for small molecules with new modes of action. Asexual reproduction of the parasite is critically dependent on the recycling of amino acids through catabolism of hemoglobin (Hb), which makes metalloaminopeptidases (MAPs) attractive targets for the development of new drugs. The Pf genome encodes eight MAPs, some of which have been found to be essential for parasite survival. In this article, we discuss the biological structure and function of each MAP within the Pf genome, along with the drug discovery efforts that have been undertaken to identify novel antimalarial candidates of therapeutic value.