Nature Biotechnology
17, 1000 - 1005 (1999)
doi:10.1038/13697
Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptidesLars C.B. Rønn1, Marianne Olsen1, Søren Østergaard2, Vladislav Kiselyov1, Vladimir Berezin1, Marie T. Mortensen3, Mathilde H. Lerche3, 4, Peter H. Jensen3, 4, Vladislav Soroka1, Jane L. Saffells5, Patrick Doherty5, Flemming M. Poulsen3, Elisabeth Bock1
& Arne Holm21
Protein Laboratory, Institute of Molecular Pathology, Panum Institute 6.2, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark. 2
Chemistry Department, Royal Agricultural and Veterinary University, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark. 3
University of Copenhagen, Institute of Molecular Biology, Department of Protein Chemistry, Øster Farimagsgade 2A, DK-1353 Copenhagen, Denmark. 4
Department of Chemistry, Carlsberg Laboratory, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark. 5
Department of Experimental Pathology, GKT School of Medicine, Guy's Hospital, London, UK.
Correspondence should be addressed to Lars C.B. Rønn lcr@plab.ku.dkcell adhesioncombinatorial chemistrydrug discoveryneural cell adhesion moleculeneurite outgrowthnuclear magnetic resonance spectroscopysurface plasmon resonancesynthetic peptideThe neural cell adhesion molecule (NCAM) plays a key role in neural development, 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 to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped 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 represent a target for discovery of nonpeptide drugs.
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