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, JM, López-Laguna, H, Parladé, E, Somma, AD, Livieri, AL, Alamo, P, Mangues, R, Unzueta, U, Villaverde, A, Vázquez, E
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p17704
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17704
http://ddd.uab.cat/record/293851
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, JMLópez-Laguna, HParladé, ESomma, ADLivieri, ALAlamo, PMangues, RUnzueta, UVillaverde, AVázquez, Ecell-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. Polypeptides incorporated into artificial secretory amyloids, by the coordination between Zn2+ and histidine-rich tails, undergo a conformation modification by which the protein gains structural stability, associated to a better secretory performance. These data offer clues for the mechanistic understanding of amyloidal depots with secretory properties and for the fabrication of high-performance versions for clinical applications. imageWILEY2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17704http://ddd.uab.cat/record/293851Advanced ScienceISSN: 21983844reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p177042026-06-14T12:41:47Z
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, JM
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, JM
López-Laguna, H
Parladé, E
Somma, AD
Livieri, AL
Alamo, P
Mangues, R
Unzueta, U
Villaverde, A
Vázquez, E
author Sánchez, JM
author_facet Sánchez, JM
López-Laguna, H
Parladé, E
Somma, AD
Livieri, AL
Alamo, P
Mangues, R
Unzueta, U
Villaverde, A
Vázquez, E
author_role author
author2 López-Laguna, H
Parladé, E
Somma, AD
Livieri, AL
Alamo, P
Mangues, R
Unzueta, U
Villaverde, A
Vázquez, E
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. Polypeptides incorporated into artificial secretory amyloids, by the coordination between Zn2+ and histidine-rich tails, undergo a conformation modification by which the protein gains structural stability, associated to a better secretory performance. These data offer clues for the mechanistic understanding of amyloidal depots with secretory properties and for the fabrication of high-performance versions for clinical applications. image
publishDate 2024
dc.date.none.fl_str_mv 2024
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17704
http://ddd.uab.cat/record/293851
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=17704
http://ddd.uab.cat/record/293851
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv Advanced Science
ISSN: 21983844
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
repository.name.fl_str_mv
repository.mail.fl_str_mv
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