Starving the Malaria Parasite:Inhibitors Active against the Aspartic Proteases Plasmepsins I,II,and IV

摘要

The most dangerous of the malaria-causing parasites,Plasmodium falciparum,infects 300-660 million people each year.The plasmepsins (PMs) are a family of Plasmodium aspartic proteases that digest human hemoglobin and deliver amino acids that are required for growth.In the search for targets for new antimalarial therapies,the mutually redundant proteolytic activity of plasmepsins for hemoglobin requires inhibitors that are broadly active against all hemoglobin-degrading plasmepsins (PM I,PM II,PM IV,and HAP)while remaining inactive against the most closely related human aspartic proteases (cathepsins D and E;hCatD and E).