Premium
Search for substrate‐based inhibitors fitting the S 2 ′ space of malarial aspartic protease plasmepsin II
Author(s) -
Kiso Aiko,
Hidaka Koushi,
Kimura Tooru,
Hayashi Yoshio,
Nezami Azin,
Freire Ernesto,
Kiso Yoshiaki
Publication year - 2004
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.609
Subject(s) - isostere , dipeptide , stereochemistry , plasmodium falciparum , protease , chemistry , residue (chemistry) , antimalarial agent , combinatorial chemistry , biochemistry , biology , enzyme , malaria , amino acid , immunology
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 P 2 ′ position in native substrates) and a bulky unit to fit the S 2 ′ pocket. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.