MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery

Benjamí Oller-Salvia, MacArena Sánchez-Navarro, Sonia Ciudad, Marc Guiu, Pol Arranz-Gibert, Cristina Garcia, Roger R. Gomis, Roméo Cecchelli, Jesús García, Ernest Giralt, Meritxell Teixidõ

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Resum

Drug 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.

Idioma originalAnglès
Pàgines (de-a)572-575
Nombre de pàgines4
RevistaAngewandte Chemie - International Edition
Volum55
Número2
DOIs
Estat de la publicacióPublicada - 11 de gen. 2016
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