TY - JOUR
T1 - Branched BBB-shuttle peptides
T2 - chemoselective modification of proteins to enhance blood-brain barrier transport
AU - Díaz-Perlas, Cristina
AU - Oller-Salvia, Benjamí
AU - Sánchez-Navarro, Macarena
AU - Teixidó, Meritxell
AU - Giralt, Ernest
N1 - Funding Information:
This work was funded by MINECO-FEDER (BIO2016-75327-R), RecerCaixa-2014-Gate2Brain and Generalitat de Catalunya (XRB, 2017SGR0998 and 2016PROD00087 – this project has been nanced with European Fund of Regional Development (FEDER)). We thank FEDAES/GENEFA and ASOGAF/BABEL FAMILY for support. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain) and the CERCA Programme of the Catalan Government. C. D.-P. holds a Predoctoral Grant Severo Ochoa (SVP-2013-067740).
Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2018
Y1 - 2018
N2 - The blood-brain barrier (BBB) hampers the delivery of therapeutic proteins into the brain. BBB-shuttle peptides have been conjugated to therapeutic payloads to increase the permeability of these molecules. However, most BBB-shuttles have several limitations, such as a lack of resistance to proteases and low effectiveness in transporting large biomolecules. We have previously reported on the THRre peptide as a protease-resistant BBB-shuttle that is able to increase the transport of fluorophores and quantum dots in vivo. In this work, we have evaluated the capacity of linear and branched THRre to increase the permeability of proteins in cellular models of the BBB. With this purpose, we have covalently attached peptides with one or two copies of the BBB-shuttle to proteins in order to develop chemically well-defined peptide-protein conjugates. While THRre does not enhance the uptake and transport of a model protein in BBB cellular models, branched THRre peptides displaying two copies of the BBB-shuttle result in a 2.6-fold increase.
AB - The blood-brain barrier (BBB) hampers the delivery of therapeutic proteins into the brain. BBB-shuttle peptides have been conjugated to therapeutic payloads to increase the permeability of these molecules. However, most BBB-shuttles have several limitations, such as a lack of resistance to proteases and low effectiveness in transporting large biomolecules. We have previously reported on the THRre peptide as a protease-resistant BBB-shuttle that is able to increase the transport of fluorophores and quantum dots in vivo. In this work, we have evaluated the capacity of linear and branched THRre to increase the permeability of proteins in cellular models of the BBB. With this purpose, we have covalently attached peptides with one or two copies of the BBB-shuttle to proteins in order to develop chemically well-defined peptide-protein conjugates. While THRre does not enhance the uptake and transport of a model protein in BBB cellular models, branched THRre peptides displaying two copies of the BBB-shuttle result in a 2.6-fold increase.
UR - http://www.scopus.com/inward/record.url?scp=85056649904&partnerID=8YFLogxK
U2 - 10.1039/c8sc02415d
DO - 10.1039/c8sc02415d
M3 - Article
AN - SCOPUS:85056649904
SN - 2041-6520
VL - 9
SP - 8409
EP - 8415
JO - Chemical Science
JF - Chemical Science
IS - 44
ER -