Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides

Peptides are experiencing a new era in medical research, finding applications ranging from therapeutics to vaccines. In spite of the promising properties of peptide pharmaceuticals, their development continues to be hindered by three weaknesses intrinsic to their structure, namely protease sensitivi...

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Detalles Bibliográficos
Autores: Arranz Gibert, Pol, Ciudad Fernández, Sonia, Seco Moral, Jesús, García Arroyo, Jesús, Giralt Lledó, Ernest, Teixidó Turà, Meritxell
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/176812
Acceso en línea:https://hdl.handle.net/2445/176812
Access Level:acceso abierto
Palabra clave:Pèptids
Farmacologia
Peptides
Pharmacology
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spelling Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptidesArranz Gibert, PolCiudad Fernández, SoniaSeco Moral, JesúsGarcía Arroyo, JesúsGiralt Lledó, ErnestTeixidó Turà, MeritxellPèptidsFarmacologiaPeptidesPharmacologyPeptides are experiencing a new era in medical research, finding applications ranging from therapeutics to vaccines. In spite of the promising properties of peptide pharmaceuticals, their development continues to be hindered by three weaknesses intrinsic to their structure, namely protease sensitivity, clearance through the kidneys, and immune system activation. Here we report on two retro-D-peptides (H2N-hrpyiah-CONH2 and H2N-pwvpswmpprht-CONH2), which are protease-resistant and retain the original BBB shuttle activity of the parent peptide but are much less immunogenic than the parent peptide. Hence, we envisage that retro-D-peptides, which display a similar topological arrangement as their parent peptides, will expand drug design and help to overcome factors that lead to the failure of peptide pharmaceuticals in pre- and clinical trials. Furthermore, we reveal requirements to avoid or elicit specific humoral responses to therapeutic peptides, which might have a strong impact in both vaccine design and peptide therapeutic agents.Nature Publishing Group2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/176812Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41598-018-24517-6Scientific Reports, 2018, vol. 8, num. 1, p. 6446https://doi.org/10.1038/s41598-018-24517-6cc-by (c) Arranz Gibert, Pol et al., 2018http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1768122026-05-27T06:46:51Z
dc.title.none.fl_str_mv Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
title Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
spellingShingle Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
Arranz Gibert, Pol
Pèptids
Farmacologia
Peptides
Pharmacology
title_short Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
title_full Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
title_fullStr Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
title_full_unstemmed Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
title_sort Immunosilencing peptides by stereochemical inversion and sequence reversal: retro-D-peptides
dc.creator.none.fl_str_mv Arranz Gibert, Pol
Ciudad Fernández, Sonia
Seco Moral, Jesús
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author Arranz Gibert, Pol
author_facet Arranz Gibert, Pol
Ciudad Fernández, Sonia
Seco Moral, Jesús
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author_role author
author2 Ciudad Fernández, Sonia
Seco Moral, Jesús
García Arroyo, Jesús
Giralt Lledó, Ernest
Teixidó Turà, Meritxell
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Pèptids
Farmacologia
Peptides
Pharmacology
topic Pèptids
Farmacologia
Peptides
Pharmacology
description Peptides are experiencing a new era in medical research, finding applications ranging from therapeutics to vaccines. In spite of the promising properties of peptide pharmaceuticals, their development continues to be hindered by three weaknesses intrinsic to their structure, namely protease sensitivity, clearance through the kidneys, and immune system activation. Here we report on two retro-D-peptides (H2N-hrpyiah-CONH2 and H2N-pwvpswmpprht-CONH2), which are protease-resistant and retain the original BBB shuttle activity of the parent peptide but are much less immunogenic than the parent peptide. Hence, we envisage that retro-D-peptides, which display a similar topological arrangement as their parent peptides, will expand drug design and help to overcome factors that lead to the failure of peptide pharmaceuticals in pre- and clinical trials. Furthermore, we reveal requirements to avoid or elicit specific humoral responses to therapeutic peptides, which might have a strong impact in both vaccine design and peptide therapeutic agents.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/2445/176812
url https://hdl.handle.net/2445/176812
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/10.1038/s41598-018-24517-6
Scientific Reports, 2018, vol. 8, num. 1, p. 6446
https://doi.org/10.1038/s41598-018-24517-6
dc.rights.none.fl_str_mv cc-by (c) Arranz Gibert, Pol et al., 2018
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Arranz Gibert, Pol et al., 2018
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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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score 15,301603

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