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

被引:122
作者
Ronn, LCB
Olsen, M
Ostergaard, S
Kiselyov, V
Berezin, V
Mortensen, MT
Lerche, MH
Jensen, PH
Soroka, V
Saffells, JL
Doherty, P
Poulsen, FM
Bock, E
Holm, A
机构
[1] Univ Copenhagen, Panum Inst 6 2, Inst Mol Pathol, Prot Lab, DK-2200 Copenhagen N, Denmark
[2] Royal Vet & Agr Univ, Dept Chem, DK-1871 Frederiksberg, Denmark
[3] Univ Copenhagen, Inst Mol Biol, Dept Prot Chem, DK-1353 Copenhagen, Denmark
[4] Carlsberg Lab, Dept Chem, DK-2500 Valby, Denmark
[5] Guys Hosp, GKT Sch Med, Dept Expt Pathol, London SE1 9RT, England
关键词
cell adhesion; combinatorial chemistry; drug discovery; neural cell adhesion molecule; neurite outgrowth; nuclear magnetic resonance spectroscopy; surface plasmon resonance; synthetic peptide;
D O I
10.1038/13697
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:1000 / 1005
页数:6
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