A possible role of N-cadherin in thalidomide teratogenicity

Several experimental findings indicate that the adhesion molecule N-cadheri n participates in distinct processes of embryogenesis that spatiotemporaril y correlate with high sensitivity to thalidomide. Therefore, we suppose tha t thalidomide might interfere with N-cadherin-mediated interactions. This h ypothesis is supported by protein-ligand docking studies simulating and cha racterizing the binding of thalidomide to N-cadherin molecules. Thalidomide was found to bind at the N-terminal domain of N-cadherin mimicking a trypt ophan residue which is critical for the homodimerization of the adhesion mo lecule. Based on these results, we suggest that thalidomide might disturb c ellular recognition and migration processes in morphogenesis by interaction with N-cadherin. (C) 2000 Elsevier Science Inc. All rights reserved.