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

Aiko Kiso, Koushi Hidaka, Tooru Kimura, Yoshio Hayashi, Azin Nezami, Ernesto I Freire, Yoshiaki Kiso

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalJournal of Peptide Science
Volume10
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

Dipeptides
Antimalarials
Plasmodium falciparum
Starvation
Hydroxyl Radical
Substrates
plasmepsin II
plasmepsin
Staphylococcus aureus auR protein
Peptide Hydrolases

Keywords

  • Allophenylnorstatine
  • Antimalarial drug
  • Aspartic protease inhibitor
  • Plasmepsin
  • Transition-state mimic

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Search for substrate-based inhibitors fitting the S2′ space of malarial aspartic protease plasmepsin II. / Kiso, Aiko; Hidaka, Koushi; Kimura, Tooru; Hayashi, Yoshio; Nezami, Azin; Freire, Ernesto I; Kiso, Yoshiaki.

In: Journal of Peptide Science, Vol. 10, No. 11, 11.2004, p. 641-647.

Research output: Contribution to journalArticle

Kiso, Aiko ; Hidaka, Koushi ; Kimura, Tooru ; Hayashi, Yoshio ; Nezami, Azin ; Freire, Ernesto I ; Kiso, Yoshiaki. / Search for substrate-based inhibitors fitting the S2′ space of malarial aspartic protease plasmepsin II. In: Journal of Peptide Science. 2004 ; Vol. 10, No. 11. pp. 641-647.
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AU - Freire, Ernesto I

AU - Kiso, Yoshiaki

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