Identification of a peptide inhibitor against glycosomal phosphoglycerate kinase of Trypanosoma brucei by a synthetic peptide library approach

Bioorg Med Chem. 1995 Mar;3(3):257-65. doi: 10.1016/0968-0896(95)00020-h.

Abstract

A synthetic peptide library, composed of 2.5 million L-amino acid pentapeptides anchored on polystyrene beads was prepared with each bead bearing a single pentapeptide sequence. This library was screened for interaction with glycosomal phosphoglycerate kinase (gPGK) of Trypanosoma brucei labelled with fluorescein or with biotin. Affinity beads that bound the enzyme were selected with a pipette or with streptavidin coated magnetic beads. The beads that bound to the enzyme were individually subjected to Edman microsequence analysis to determine the sequence of the corresponding peptide ligands. The corresponding peptide-sequences were synthesised as free peptide acids and evaluated for enzyme activity inhibition. The pentapeptide NWMMF was able to selectively inhibit gPGK with an IC50 of approximately 80 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins
  • Biotin
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Fluorescein
  • Fluoresceins
  • Glycolysis / drug effects
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / isolation & purification
  • Oligopeptides / pharmacology*
  • Phosphoglycerate Kinase / antagonists & inhibitors*
  • Streptavidin
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Affinity Labels
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Fluoresceins
  • Oligopeptides
  • Biotin
  • Streptavidin
  • Phosphoglycerate Kinase
  • Fluorescein