A possible role of N-cadherin in thalidomide teratogenicity

Life Sci. 2000 Jun 16;67(4):457-61. doi: 10.1016/s0024-3205(00)00636-6.

Abstract

Several experimental findings indicate that the adhesion molecule N-cadherin participates in distinct processes of embryogenesis that spatiotemporarily correlate with high sensitivity to thalidomide. Therefore, we suppose that thalidomide might interfere with N-cadherin-mediated interactions. This hypothesis is supported by protein-ligand docking studies simulating and characterizing the binding of thalidomide to N-cadherin molecules. Thalidomide was found to bind at the N-terminal domain of N-cadherin mimicking a tryptophan residue which is critical for the homodimerization of the adhesion molecule. Based on these results, we suggest that thalidomide might disturb cellular recognition and migration processes in morphogenesis by interaction with N-cadherin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Abnormalities, Drug-Induced / metabolism
  • Animals
  • Cadherins / physiology*
  • Chick Embryo
  • Models, Molecular
  • Molecular Structure
  • Teratogens / chemistry
  • Teratogens / metabolism
  • Teratogens / toxicity*
  • Thalidomide / chemistry
  • Thalidomide / metabolism
  • Thalidomide / toxicity*
  • Tryptophan / chemistry

Substances

  • Cadherins
  • Teratogens
  • Thalidomide
  • Tryptophan