Identification
of Potent and Selective Non-covalent
Inhibitors of the Plasmodium falciparum Proteasome
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Abstract
We
have identified short N,C-capped peptides that selectively inhibit
the proteasome of the malaria-causing pathogen Plasmodium
falciparum. These compounds are highly potent in culture
with no toxicity in host cells. One cyclic biphenyl ether compound
inhibited intraerythrocytic growth of P. falciparum with an IC<sub>50</sub> of 35 nM, and we show that even a pulse
treatment with this cyclic peptide induced parasite death due to proteasome
inhibition. These compounds represent promising new antimalarial agents
that target the essential proteasomal machinery of the parasite without
toxicity toward the host