TY - JOUR
T1 - Phage display as a tool to discover blood–brain barrier (BBB)-shuttle peptides
T2 - panning against a human BBB cellular model
AU - Díaz-Perlas, Cristina
AU - Sánchez-Navarro, Macarena
AU - Oller-Salvia, Benjamí
AU - Moreno, Miguel
AU - Teixidó, Meritxell
AU - Giralt, Ernest
N1 - Funding Information:
This work was financially supported by MINECO-FEDER (BIO2013-40716-R), RecerCaixa-2014-Gate2Brain, and Generalitat de Catalunya (XRB and 2014-SGR-521). We thank FARA, FEDAES/GENEFA for support. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain). C.D.-P. and M.S.-N. hold a Predoctoral Grant Severo Ochoa (SVP-2013-067740) and Juan de la Cierva fellowship, respectively.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - BBB-shuttle peptides
KW - blood–brain barrier
KW - blood–brain barrier cellular model
KW - phage display
UR - http://www.scopus.com/inward/record.url?scp=85010843603&partnerID=8YFLogxK
U2 - 10.1002/bip.22928
DO - 10.1002/bip.22928
M3 - Article
C2 - 27486695
AN - SCOPUS:85010843603
SN - 0006-3525
VL - 108
JO - Biopolymers
JF - Biopolymers
IS - 1
M1 - e22928
ER -