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MiniAp‐4: A Venom‐Inspired Peptidomimetic for Brain Delivery
Author(s) -
OllerSalvia Benjamí,
SánchezNavarro Macarena,
Ciudad Sonia,
Guiu Marc,
ArranzGibert Pol,
Garcia Cristina,
Gomis Roger R.,
Cecchelli Roméo,
García Jesús,
Giralt Ernest,
Teixidó Meritxell
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201508445
Subject(s) - peptidomimetic , blood–brain barrier , venom , immunogenicity , protease , drug delivery , neurotoxin , apamin , chemistry , pharmacology , biology , neuroscience , biophysics , central nervous system , biochemistry , peptide , immunology , immune system , enzyme , potassium channel , organic chemistry
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.