Oller Salvia, BenjamíSánchez Navarro, MacarenaCiudad Fernández, SoniaGuiu, MarcArranz Gibert, PolGarcía, CristinaGomis i Cabré, RogerCecchelli, RoméoGarcía Arroyo, JesúsGiralt Lledó, ErnestTeixidó Turà, Meritxell2016-11-142016-11-142016-01-050003-3022https://hdl.handle.net/2445/103642Drug delivery across the blood-brain barrier (BBB) is a formidable challenge for therapies targeting the central nervous system. Although BBB shuttle peptides enhance transport into the brain non-invasively, their application is partly limited by lability to proteases. The present study proposes the use of cyclic peptides derived from venoms as an affordable way to circumvent this drawback. Apamin, a neurotoxin from bee venom, was minimized by reducing its complexity, toxicity, and immunogenicity, while preserving brain targeting, active transport, and protease resistance. Among the analogues designed, the monocyclic lactam-bridged peptidomimetic MiniAp-4 was the most permeable. This molecule is capable of translocating proteins and nanoparticles in a human-cell-based BBB model. Furthermore, MiniAp-4 can efficiently deliver a cargo across the BBB into the brain parenchyma of mice.4 p.application/pdfengcc-by-nc-nd (c) Oller Salvia, Benjamí et al., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esVerins animalsSíntesi de pèptidsMalalties cerebralsVenomPeptide synthesisBrain diseasesinfo:eu-repo/semantics/article6570162016-11-14info:eu-repo/semantics/openAccess26492861