title: Phage display as a tool to discover blood-brain barrier (BBB)-shuttle peptides: panning against a human BBB cellular model.
abstract: 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.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Díaz-Perlas
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Macarena
authors.initials: M
authors.lastname: Sánchez-Navarro
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Benjamí
authors.initials: B
authors.lastname: Oller-Salvia
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Moreno
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Teixidó
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, Barcelona, 08028, Spain.|Department of Organic Chemistry, University of Barcelona, Martí i Franquès 1-11, Barcelona, 08028, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008954:Models, Biological; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D017422:Sequence Analysis, DNA
chemical_list: D019151:Peptide Library; D010455:Peptides; D049452:Green Fluorescent Proteins
keywords: BBB-shuttle peptides; blood-brain barrier; blood-brain barrier cellular model; phage display