Identification of a 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-NH(2) 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 10.7microM, 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-NH(2) should prove useful for studies designed to evaluate N-cadherin function in various biological processes.
Devemy
Emmanuelle
E
Division of Urology, Department of Surgery, McGill University, Urology Research Laboratories, Royal Victoria Hospital, Room H6.15, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada. emmanuelle.devemy@mcgill.ca
Blaschuk
Orest W
OW
D015820:Cadherins / Q000037:antagonists & inhibitors*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D009842:Oligopeptides / Q000302:isolation & purification* / Q000494:pharmacology*; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D020349:Surface Plasmon Resonance
D015820:Cadherins; D007141:Immunoglobulin Fc Fragments; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C539764:seryl-tryptophyl-threonyl-leucyl-tyrosyl-threonyl-prolyl-seryl-glycyl-glutaminyl-seryl-lysine