Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/75096 |
Resumo: | The self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer’s disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils. |
id |
RCAP_57d96f439cc44f110cfb3b6a5cd3e6d9 |
---|---|
oai_identifier_str |
oai:repositorium.sdum.uminho.pt:1822/75096 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic formsAlzheimer’s diseaseAmyloid-βDendrimersGallic acidSupramolecular assemblyamyloid-betaScience & TechnologyThe self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer’s disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils.The authors acknowledge the financial support from the EC (FORECAST-668983), “Programa Operacional Regional do Norte”, “Fundo Social Europeu”, Norte2020 TERM&SC, for the PhD grant NORTE-08-5369-FSE-000044, the Spanish Ministry of Science and Innovation (RTI2018-102212-B-I00), the Xunta de Galicia (ED431C 2018/30; Centro singular de investigación de Galicia accreditation 2019−2022, ED431G 2019/03), European Regional Development Fund-ERDF, and the Galician Supercomputing Centre (CESGA) and the MAT2016-80266-R of the Spanish Ministry of Science and Innovation.ACS PublicationsUniversidade do MinhoAraújo, Ana Rita RodriguesCorrea, JuanDomínguez-Arca, VicenteReis, R. L.Fernandez-Megia, EduardoPires, R. A.2021-122021-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/75096engAraújo A. R., Correa J., Domínguez-Arca V., Reis R. L., Fernandez-Megia E., Pires R. A. Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms, ACS Applied Materials & Interfaces, Vol. 13, Issue 50, pp. 59673–59682, doi:10.1021/acsami.1c17823, 20211944-824410.1021/acsami.1c1782334874691https://doi.org/10.1021/acsami.1c17823info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:26:40Zoai:repositorium.sdum.uminho.pt:1822/75096Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:21:08.704684Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
title |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
spellingShingle |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms Araújo, Ana Rita Rodrigues Alzheimer’s disease Amyloid-β Dendrimers Gallic acid Supramolecular assembly amyloid-beta Science & Technology |
title_short |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
title_full |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
title_fullStr |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
title_full_unstemmed |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
title_sort |
Functional gallic acid-based dendrimers as synthetic nanotools to remodel amyloid-β-42 into noncytotoxic forms |
author |
Araújo, Ana Rita Rodrigues |
author_facet |
Araújo, Ana Rita Rodrigues Correa, Juan Domínguez-Arca, Vicente Reis, R. L. Fernandez-Megia, Eduardo Pires, R. A. |
author_role |
author |
author2 |
Correa, Juan Domínguez-Arca, Vicente Reis, R. L. Fernandez-Megia, Eduardo Pires, R. A. |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Araújo, Ana Rita Rodrigues Correa, Juan Domínguez-Arca, Vicente Reis, R. L. Fernandez-Megia, Eduardo Pires, R. A. |
dc.subject.por.fl_str_mv |
Alzheimer’s disease Amyloid-β Dendrimers Gallic acid Supramolecular assembly amyloid-beta Science & Technology |
topic |
Alzheimer’s disease Amyloid-β Dendrimers Gallic acid Supramolecular assembly amyloid-beta Science & Technology |
description |
The self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer’s disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12 2021-12-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/75096 |
url |
http://hdl.handle.net/1822/75096 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Araújo A. R., Correa J., Domínguez-Arca V., Reis R. L., Fernandez-Megia E., Pires R. A. Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms, ACS Applied Materials & Interfaces, Vol. 13, Issue 50, pp. 59673–59682, doi:10.1021/acsami.1c17823, 2021 1944-8244 10.1021/acsami.1c17823 34874691 https://doi.org/10.1021/acsami.1c17823 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
ACS Publications |
publisher.none.fl_str_mv |
ACS Publications |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799132677422448640 |