Computational design of novel peptidomimetic inhibitors of cadherin homophilic interactions

Org Biomol Chem. 2015 Mar 7;13(9):2570-3. doi: 10.1039/c4ob02538e.

Abstract

We report a first set of peptidomimetic ligands mimicking the adhesive interface identified by recent crystallographic structures of E- and N-cadherin. Compounds 2 and 3 inhibit adhesion of epithelial ovarian cancer (EOC) cells with improved efficacy compared to the ADH-1 peptide, a N-cadherin antagonist that is in early clinical trials in EOC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / antagonists & inhibitors*
  • Carcinoma, Ovarian Epithelial
  • Cell Adhesion / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / pathology
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Peptidomimetics*
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cadherins
  • Ligands
  • Oligopeptides
  • Peptidomimetics
  • Small Molecule Libraries