Branched BBB-shuttle peptides: chemoselective modification of proteins to enhance blood-brain barrier transport

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

Producció científica: Article en revista indexadaArticleAvaluat per experts

38 Cites (Scopus)

Resum

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.

Idioma originalAnglès
Pàgines (de-a)8409-8415
Nombre de pàgines7
RevistaChemical Science
Volum9
Número44
DOIs
Estat de la publicacióPublicada - 2018
Publicat externament

Fingerprint

Navegar pels temes de recerca de 'Branched BBB-shuttle peptides: chemoselective modification of proteins to enhance blood-brain barrier transport'. Junts formen un fingerprint únic.

Com citar-ho