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


  • F.H. thanks the Novartis Foundation and the Human Frontier Science Program for financial support. This research was supported by the ETH Research Council. We thank Anna Oksman for technical assistance.


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Clamping down: A new class of aspartic protease inhibitors that target the malarial protease family Plasmepsin are reported. These ligands utilize a novel “diamine clamp” to engage the catalytic dyad. They are potent inhibitors of plasmepsins I, II, and IV, while retaining good selectivity against the closely related human cathepsins D and E.