Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides

The neural cell adhesion molecule (NCAM) plays a key role in neural develop ment, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical t o that activated by hemophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1, By nuclear magneti c resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was ma pped and shown to be different from the binding site of the NCAM Ig2 module . The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may repre sent a target for discovery of nonpeptide drugs.