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

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...

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Autores: Oller Salvia, Benjamí, Sánchez Navarro, Macarena, Ciudad Fernández, Sonia, Guiu, Marc, Arranz Gibert, Pol, García, Cristina, Gomis i Cabré, Roger, Cecchelli, Roméo, García Arroyo, Jesús, Giralt Lledó, Ernest, Teixidó Turà, Meritxell
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/103642
Acceso en línea:https://hdl.handle.net/2445/103642
Access Level:acceso abierto
Palabra clave:Verins animals
Síntesi de pèptids
Malalties cerebrals
Venom
Peptide synthesis
Brain diseases
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spelling MiniAp-4: A Venom-Inspired Peptidomimetic for Brain DeliveryOller Salvia, BenjamíSánchez Navarro, MacarenaCiudad Fernández, SoniaGuiu, MarcArranz Gibert, PolGarcía, CristinaGomis i Cabré, RogerCecchelli, RoméoGarcía Arroyo, JesúsGiralt Lledó, ErnestTeixidó Turà, MeritxellVerins animalsSíntesi de pèptidsMalalties cerebralsVenomPeptide synthesisBrain diseasesDrug 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.Wiley2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/103642Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/anie.201508445Angewandte Chemie International Edition, 2016, vol. 55, num. 2, p. 572-575https://doi.org/10.1002/anie.201508445cc-by-nc-nd (c) Oller Salvia, Benjamí et al., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1036422026-05-27T06:46:51Z
dc.title.none.fl_str_mv MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
title MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
spellingShingle MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
Oller Salvia, Benjamí
Verins animals
Síntesi de pèptids
Malalties cerebrals
Venom
Peptide synthesis
Brain diseases
title_short MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
title_full MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
title_fullStr MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
title_full_unstemmed MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
title_sort MiniAp-4: A Venom-Inspired Peptidomimetic for Brain Delivery
dc.creator.none.fl_str_mv Oller Salvia, Benjamí
Sánchez Navarro, Macarena
Ciudad Fernández, Sonia
Guiu, Marc
Arranz Gibert, Pol
García, Cristina
Gomis i Cabré, Roger
Cecchelli, Roméo
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author Oller Salvia, Benjamí
author_facet Oller Salvia, Benjamí
Sánchez Navarro, Macarena
Ciudad Fernández, Sonia
Guiu, Marc
Arranz Gibert, Pol
García, Cristina
Gomis i Cabré, Roger
Cecchelli, Roméo
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author_role author
author2 Sánchez Navarro, Macarena
Ciudad Fernández, Sonia
Guiu, Marc
Arranz Gibert, Pol
García, Cristina
Gomis i Cabré, Roger
Cecchelli, Roméo
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Verins animals
Síntesi de pèptids
Malalties cerebrals
Venom
Peptide synthesis
Brain diseases
topic Verins animals
Síntesi de pèptids
Malalties cerebrals
Venom
Peptide synthesis
Brain diseases
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/103642
url https://hdl.handle.net/2445/103642
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/anie.201508445
Angewandte Chemie International Edition, 2016, vol. 55, num. 2, p. 572-575
https://doi.org/10.1002/anie.201508445
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Oller Salvia, Benjamí et al., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Oller Salvia, Benjamí et al., 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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