Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3048-52. doi: 10.1016/j.bmcl.2007.03.052. Epub 2007 Mar 21.

Abstract

Based on a highly potent allophenylnorstatine-containing inhibitor, KNI-10006, against the plasmepsins of Plasmodium falciparum, we synthesized a series of tripeptide-type compounds with various N-terminal moieties and evaluated their inhibitory activities against plasmepsin II. Certain phenylacetyl derivatives exhibited extremely high affinity with K(i) values of less than 0.1n M suggesting successful hydrophobic interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / chemistry
  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology
  • Phenylbutyrates / chemistry*
  • Plasmodium falciparum / enzymology*
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Protein Conformation
  • Protozoan Proteins
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • KNI 10006
  • Oligopeptides
  • Phenylbutyrates
  • Protease Inhibitors
  • Protozoan Proteins
  • 3-amino-2-hydroxy-4-phenylbutanoic acid
  • Aspartic Acid Endopeptidases
  • plasmepsin II