Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids

Developing time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non-toxic microscale amyloid materials through the coordination between divalent metals and poly-histidine s...

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Autores: Sánchez, Julieta M.|||0000-0001-6676-5776, López-Laguna, Hèctor|||0000-0001-5249-8304, Parladé Molist, Eloi|||0000-0001-5750-550X, Di Somma, Angela|||0000-0003-4916-7875, Livieri, Andrea|||0000-0002-0724-373X, Álamo, Patricia|||0000-0003-0510-5701, Mangues, Ramon|||0000-0003-2661-9525, Unzueta Elorza, Ugutz|||0000-0001-5119-2266, Villaverde, Antonio|||0000-0002-2615-4521, Vázquez, Esther|||0000-0003-1052-0424
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:293851
Acceso en línea:https://ddd.uab.cat/record/293851
https://dx.doi.org/urn:doi:10.1002/advs.202309427
Access Level:acceso abierto
Palabra clave:Cell-targeting
Drug delivery
Microparticles
Nanoparticles
Recombinant proteins
Secretory granules
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spelling Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory AmyloidsSánchez, Julieta M.|||0000-0001-6676-5776López-Laguna, Hèctor|||0000-0001-5249-8304Parladé Molist, Eloi|||0000-0001-5750-550XDi Somma, Angela|||0000-0003-4916-7875Livieri, Andrea|||0000-0002-0724-373XÁlamo, Patricia|||0000-0003-0510-5701Mangues, Ramon|||0000-0003-2661-9525Unzueta Elorza, Ugutz|||0000-0001-5119-2266Villaverde, Antonio|||0000-0002-2615-4521Vázquez, Esther|||0000-0003-1052-0424Cell-targetingDrug deliveryMicroparticlesNanoparticlesRecombinant proteinsSecretory granulesDeveloping time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non-toxic microscale amyloid materials through the coordination between divalent metals and poly-histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self-disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time-sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein-only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein-recruiting/protein-releasing granular depots. 22024-01-0120242024-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/293851https://dx.doi.org/urn:doi:10.1002/advs.202309427reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133858-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-136845OB-I00Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-116174RB-I00Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00150Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00400open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2938512026-06-06T12:50:31Z
dc.title.none.fl_str_mv Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
title Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
spellingShingle Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
Sánchez, Julieta M.|||0000-0001-6676-5776
Cell-targeting
Drug delivery
Microparticles
Nanoparticles
Recombinant proteins
Secretory granules
title_short Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
title_full Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
title_fullStr Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
title_full_unstemmed Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
title_sort Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids
dc.creator.none.fl_str_mv Sánchez, Julieta M.|||0000-0001-6676-5776
López-Laguna, Hèctor|||0000-0001-5249-8304
Parladé Molist, Eloi|||0000-0001-5750-550X
Di Somma, Angela|||0000-0003-4916-7875
Livieri, Andrea|||0000-0002-0724-373X
Álamo, Patricia|||0000-0003-0510-5701
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
author Sánchez, Julieta M.|||0000-0001-6676-5776
author_facet Sánchez, Julieta M.|||0000-0001-6676-5776
López-Laguna, Hèctor|||0000-0001-5249-8304
Parladé Molist, Eloi|||0000-0001-5750-550X
Di Somma, Angela|||0000-0003-4916-7875
Livieri, Andrea|||0000-0002-0724-373X
Álamo, Patricia|||0000-0003-0510-5701
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
author_role author
author2 López-Laguna, Hèctor|||0000-0001-5249-8304
Parladé Molist, Eloi|||0000-0001-5750-550X
Di Somma, Angela|||0000-0003-4916-7875
Livieri, Andrea|||0000-0002-0724-373X
Álamo, Patricia|||0000-0003-0510-5701
Mangues, Ramon|||0000-0003-2661-9525
Unzueta Elorza, Ugutz|||0000-0001-5119-2266
Villaverde, Antonio|||0000-0002-2615-4521
Vázquez, Esther|||0000-0003-1052-0424
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cell-targeting
Drug delivery
Microparticles
Nanoparticles
Recombinant proteins
Secretory granules
topic Cell-targeting
Drug delivery
Microparticles
Nanoparticles
Recombinant proteins
Secretory granules
description Developing time-sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non-toxic microscale amyloid materials through the coordination between divalent metals and poly-histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self-disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time-sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein-only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein-recruiting/protein-releasing granular depots.
publishDate 2024
dc.date.none.fl_str_mv 2
2024-01-01
2024
2024-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/293851
https://dx.doi.org/urn:doi:10.1002/advs.202309427
url https://ddd.uab.cat/record/293851
https://dx.doi.org/urn:doi:10.1002/advs.202309427
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2019-105416RB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PDC2022-133858-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2022-136845OB-I00
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-116174RB-I00
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI21/00150
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI20/00400
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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