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

Research output: Indexed journal article Articlepeer-review

70 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)572-575
Number of pages4
JournalAngewandte Chemie - International Edition
Volume55
Issue number2
DOIs
Publication statusPublished - 11 Jan 2016
Externally publishedYes

Keywords

  • apamin
  • blood-brain barrier
  • drug delivery
  • peptides

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