Discovery of a potent peptidic cyclophilin A inhibitor Trp-Gly-Pro

Eur J Med Chem. 2011 May;46(5):1701-5. doi: 10.1016/j.ejmech.2011.02.023. Epub 2011 Feb 22.

Abstract

Through virtual screening of a rationally built database consisting of 40 peptides, we identified three short peptides. After testing these three synthetic peptides, we found that the peptide Trp-Gly-Pro (WGP) showed comparable inhibitory ability as positive control cyclosporine A (CsA) on CypA-mediated PPIase activity with IC50 values of 33.11 nM and 10.25 nM, respectively. The peptide WGP had same order of CypA-binding affinity as CsA with dissociation equilibrium constant KD of 3.41×10(-6) and 6.42×10(-6) M, respectively. This peptide could also inhibit HIV-1IIIB infection. This study provides a novel strategy for rational design and development of peptidic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / drug effects
  • Cell Line, Transformed
  • Cyclophilin A / antagonists & inhibitors*
  • Cyclophilin A / metabolism
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • HIV Infections / drug therapy
  • HIV-1 / drug effects
  • Humans
  • Models, Molecular
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Structure-Activity Relationship
  • Virus Replication / drug effects

Substances

  • Oligopeptides
  • Cyclophilin A