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- Title
MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery.
- Authors
Oller ‐ Salvia, Benjamí; Sánchez ‐ Navarro, Macarena; Ciudad, Sonia; Guiu, Marc; Arranz ‐ Gibert, Pol; Garcia, Cristina; Gomis, Roger R.; Cecchelli, Roméo; García, Jesús; Giralt, Ernest; Teixidó, Meritxell
- Abstract
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 lactambridged 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.
- Subjects
DRUG delivery systems; BLOOD-brain barrier; CENTRAL nervous system; PHYSIOLOGICAL effects of venom; PROTEASE inhibitors
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 2, p582
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201508445