Identification of novel N-cadherin antagonist

The cell adhesion molecule, N-cadherin plays a pivotal role in many biological and disease processes. Drugs that modulate N-cadherin function should therefore be useful therapeutic agents. We have used phage display technology to identify amino acid sequences capable of binding to N-cadherin. All of these sequences harbor a Trp residue in the second position from the N-terminus. A synthetic linear peptide containing one of these sequences, H-SWTLYTPSGQSK-NH2 was found to bind a chimeric protein composed of the N-cadherin ectodomain fused to the immunoglobulin G1 Fc fragment with an affinity (K-D) of 10.7 mu M, as determined by surface plasmon resonance. It also blocked the aggregation of beads coated with this chimeric protein. Furthermore, this peptide disrupted adhesion and tube formation by N-cadherin-expressing human umbilical vein endothelial cells in vitro. These observations suggest that N-cadherin antagonists have the potential of serving as anti-angiogenic agents. The peptide, H-SWTLYTPSGQSK-NH2 should prove useful for studies designed to evaluate N-cadherin function in various biological processes. (C) 2008 Elsevier Inc. All rights reserved.