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2016-01-05

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cc-by-nc-nd (c) Oller Salvia, Benjamí et al., 2016
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/103642

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

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https://doi.org/10.1002/anie.201508445

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.

Subject

Verins animals, Síntesi de pèptids, Malalties cerebrals

Subject (English)

Venom, Peptide synthesis, Brain diseases

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Articles publicats en revistes (Química Inorgànica i Orgànica)
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citation

OLLER SALVIA, Benjamí, et al. MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery. Angewandte Chemie International Edition. 2016. Vol. 55, num. 2, pags. 572-575. ISSN 0003-3022. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/103642

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