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Targeting the Plasmepsin 4 Orthologs of Plasmodium sp. with “Double Drug” Inhibitors

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Plasmepsin 4 (PM4) is a digestive vacuole enzyme found in all Plasmodium species examined to date. While P. falciparum has three additional aspartic proteinases in its digestive vacuole in addition to plasmepsin 4, other Plasmodium species have only PM4 in their digestive vacuole. Therefore, PM4 may be a good target for the development of an antimalarial drug. This study presents data obtained with PM4s from several Plasmodium species. Low nanomolar Ki values have been observed for all PM4s studied.

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Keywords: Double Drug; Plasmepsin; Proenzyme; a combination of two molecular entities in one compound that kill a pathogen by two mechanisms; a compound that blocks the growth of the malarial parasite in culture; a word derived from Plasmodium pepsin; antimalarial; proteolytic enzyme from the Plasmodium species; statine; the naturallyoccurring amino acid derivative (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid

Document Type: Research Article

Publication date: 2008-09-01

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  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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