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. 1991 Nov;88(5):1467–1472. doi: 10.1172/JCI115456

Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase.

P J Rosenthal 1, W S Wollish 1, J T Palmer 1, D Rasnick 1
PMCID: PMC295650  PMID: 1939639

Abstract

We previously identified a Plasmodium falciparum trophozoite cysteine proteinase (TCP) and hypothesized that it is required for the degradation of host hemoglobin by intraerythrocytic malaria parasites. To test this hypothesis and to evaluate TCP as a chemotherapeutic target, we examined the antimalarial effects of a panel of peptide fluoromethyl ketone proteinase inhibitors. For each inhibitor, effectiveness at inhibiting the activity of TCP correlated with effectiveness at both blocking hemoglobin degradation and killing cultured parasites. Benzyloxycarbonyl (Z)-Phe-Arg-CH2F, the most potent inhibitor, inhibited TCP at picomolar concentrations and blocked hemoglobin degradation and killed parasites at nanomolar concentrations. Micromolar concentrations of the inhibitor were nontoxic to cultured mammalian cells. These results support the hypothesis that TCP is a necessary hemoglobinase and suggest that it is a promising chemotherapeutic target.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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