Phage display as a tool to discover blood–brain barrier (BBB)-shuttle peptides: panning against a human BBB cellular model

Cristina Díaz-Perlas, Macarena Sánchez-Navarro, Benjamí Oller-Salvia, Miguel Moreno, Meritxell Teixidó, Ernest Giralt

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Resum

Most potential drugs for the treatment of central nervous system disorders do not cross the blood–brain barrier (BBB). Much research effort has been devoted to the discovery of new BBB-shuttle peptides—most of which have been identified by phage display. Here we report for the first time on the use of phage display against a human BBB cellular model which mimics the characteristics of the BBB. From the panning experiment of a 12-mer library, the SGVYKVAYDWQH (SGV) peptide sequence was selected and its permeability validated in the aforementioned model. Furthermore, internalization studies suggested that SGV internalizes through a clathrin-mediated mechanism and that it increases the uptake of a cargo in endothelial cells. These results highlight the usefulness of in vitro BBB models for the discovery of BBB-shuttle peptides through phage display libraries.

Idioma originalAnglès
Número d’articlee22928
RevistaBiopolymers
Volum108
Número1
DOIs
Estat de la publicacióPublicada - 1 de gen. 2017
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