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J. Biol. Chem., Vol. 279, Issue 29, 30707-30714, July 16, 2004

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Selection of Poly- 2,8-Sialic Acid Mimotopes from a Random Phage Peptide Library and Analysis of Their Bioactivity^*

Pascal Torregrossa, Lone Buhl¶||, Mircea Bancila||, Pascale Durbec, Claus Schafer¶, Melitta Schachner**, and Geneviève Rougon

From the 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 Cedex 9, France, ^¶Schafer-N. Fruebjergen, 2100 Copenhagen, Denmark, and ^**Zentrum für Molekulare Neurobiologie, Universitat Hamburg, 20251 Hamburg, Germany

Poly- 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.

Received for publication, April 8, 2004 , and in revised form, May 5, 2004.

^* This work was supported by the CNRS, Ministre de la Recherche (Action Concertée Incitative Molécules et Cibles Thérapeutiques), European Union (Quality of Life program Key Action) Grant QLRT 1999-02187 (to M. S., C. S., and G. R.), and by European Community Grant QLG3-CT-2000-00911 (to G. R., P. D., and M. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a Ligue contre le Cancer fellowship.

^|| Both authors contributed equally to this work.

To whom correspondence should be addressed. Tel.: 33-49-126-9348; Fax: 33-49-126-9748; E-mail: rougon{at}ibdm.univ-mrs.fr.

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