Functional Profiling, Identification, and Inhibition of Plasmepsins in Intraerythrocytic Malaria Parasites

Abstract

Plasmepsins (PMs), aspartic proteases required for malaria-parasite growth, are promising antimalarial targets. The in situ screening of PMs with probes formed from β-hydroxyazides 1 and alkynes with a photo-cross-linking unit and a tetraethylrhodamine reporter led to the identification of the small-molecule inhibitor 2, which inhibits all four food-vacuole PMs and showed potent antimalarial activity in red-blood-cell cultures.