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

Lars C.B. Rønn, Mariann Olsen, Søren Østergaard, Vladimir Kiselyov, Vladimir Berezin, Marie T Mortensen, Mathilde Hauge Lerche, Peter H. Jensen, Vladislav Soroka, Jane L. Saffells, Patrick Doherty, Flemming M Poulsen, Elisabeth Bock, Arne Holm

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The 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.
Original languageEnglish
JournalNature Biotechnology
Volume17
Issue number10
Pages (from-to)1000-1005
Number of pages6
ISSN1087-0156
DOIs
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • Cell Adhesion Molecules, Neuronal
  • Combinatorial Chemistry Techniques
  • Consensus Sequence
  • Immunoglobulins
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Neurites
  • Peptide Library
  • Peptides
  • Signal Transduction
  • Surface Plasmon Resonance
  • Microbiology
  • Cell adhesion
  • Combinatorial chemistry
  • Drug discovery
  • Neural cell adhesion molecule
  • Neurite outgrowth
  • Nuclear magnetic resonance spectroscopy
  • Surface plasmon resonance
  • Synthetic peptide
  • ligand
  • nerve cell adhesion molecule
  • peptide
  • synthetic peptide
  • animal cell
  • article
  • binding site
  • cell adhesion
  • cell culture
  • controlled study
  • embryo
  • gene mapping
  • nerve cell
  • nerve fiber growth
  • nonhuman
  • nuclear magnetic resonance spectroscopy
  • priority journal
  • protein analysis
  • rat
  • signal transduction
  • Complement C3
  • BIOTECHNOLOGY
  • LONG-TERM POTENTIATION
  • N-CAM
  • NEURITE OUTGROWTH
  • NCAM
  • BINDING
  • FGF
  • RECEPTOR
  • RAT
  • PROLIFERATION
  • SPECTROSCOPY
  • combinatorial chemistry
  • drug discovery
  • neural cell adhesion molecule
  • neurite outgrowth
  • surface plasmon resonance
  • biotechnology
  • neural cell adhesion molecule analysis, functions
  • neuritogenic ligands analysis, applications, identification
  • peptides synthesis
  • synthetic peptides analysis, applications
  • 02506, Cytology - Animal
  • 10054, Biochemistry methods - Proteins, peptides and amino acids
  • 10502, Biophysics - General
  • 10506, Biophysics - Molecular properties and macromolecules
  • 12002, Physiology - General
  • 13012, Metabolism - Proteins, peptides and amino acids
  • 17002, Endocrine - General
  • 20501, Nervous system - General and methods
  • 22002, Pharmacology - General
  • 32500, Tissue culture, apparatus, methods and media
  • 32600, In vitro cellular and subcellular studies
  • hippocampal cells nervous system
  • neurons nervous system
  • cell culture Cell Culture Techniques, culture method
  • combinatorial libraries Synthesis/Modification Techniques, applications, synthetic method
  • NMR spectroscopy: analytical method, spectroscopic techniques CB
  • peptide synthesis Synthesis/Modification Techniques, synthetic method
  • surface plasmon resonance analysis: Analysis/Characterization Techniques CB, analytical method
  • Biochemistry and Molecular Biophysics
  • Methods and Techniques
  • Pharmacology
  • CELL adhesion molecules

Cite this

Rønn, L. C. B., Olsen, M., Østergaard, S., Kiselyov, V., Berezin, V., Mortensen, M. T., Lerche, M. H., Jensen, P. H., Soroka, V., Saffells, J. L., Doherty, P., Poulsen, F. M., Bock, E., & Holm, A. (1999). Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides. Nature Biotechnology, 17(10), 1000-1005. https://doi.org/10.1038/13697