Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II.

Abstract

Plasmepsin (Plm) has been identified as an important target for the development of new antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state mimic were synthesized. The general design principle was provision of a conformationally restrained hydroxyl group (corresponding to the set residue at the P2' position in native substrates) and a bulky unit to fit the S2' pocket.

• Authors: Aiko Kiso, Koushi Hidaka, Tooru Kimura, Yoshio Hayashi, Azin Nezami, Ernesto Freire, Yoshiaki Kiso
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 10 Issue 11 Pg. 641-7 (Nov 2004) ISSN: 1075-2617 [Print] England
• PMID: 15568678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Oligopeptides
• Protozoan Proteins
• Aspartic Acid Endopeptidases
• plasmepsin II

Topics

• Animals
• Aspartic Acid Endopeptidases (antagonists & inhibitors, chemistry)
• Binding Sites
• Enzyme Inhibitors (chemistry, pharmacology)
• Molecular Mimicry
• Oligopeptides (chemistry, pharmacology)
• Plasmodium falciparum (enzymology)
• Protozoan Proteins
• Structure-Activity Relationship