Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity.
Poly-alpha 2-8 sialic acid (PSA), attached to the neural cell adhesion molecule, is a permissive determinant for numerous morphogenetic and neural plasticity processes, making it a potential therapeutic target. Here, using a monoclonal antibody specific for PSA, we screened a phage-display library and identified two cyclic nine-amino acid peptides (p1, p2) that are PSA epitope analogues. We evaluated their bioactivity in vitro and in vivo. In culture, micromolar concentrations of the peptides promoted axon growth, defasciculation, and migration of neural progenitors. When injected into developing chicken retina, the peptides modified the trajectory of retinal ganglion cell axons. Moreover, they enhanced migration of grafted neuroblasts in mouse brain. These effects were selective and dependent upon the presence of PSA on transplanted cells. Our results demonstrate the feasibility and therapeutic potential of enhancing PSA biological activity.
Torregrossa
Pascal
P
Laboratoire de Neurogenèse et Morphogenèse dans le Développement et chez l'Adulte, Unité Mixte de Recherche CNRS 6156, Université de la Méditerranée, Institut de Biologie du Développement, Parc Scientifique de Luminy, 13288 Marseille 9, France.
Buhl
Lone
L
Bancila
Mircea
M
Durbec
Pascale
P
Schafer
Claus
C
Schachner
Melitta
M
Rougon
Geneviève
G
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002465:Cell Movement; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009345:Neisseria meningitidis / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010452:Peptide Biosynthesis; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D012160:Retina / Q000196:embryology / Q000378:metabolism*; D012794:Sialic Acids / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D019151:Peptide Library; D010455:Peptides; D012794:Sialic Acids; C071290:alpha(2-8)polysialic acid