Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)

Detalhes bibliográficos
Autor(a) principal: Posado-Fernández, Adrián
Data de Publicação: 2019
Outros Autores: Afonso, Cláudia F., Dória, Gonçalo, Flores, Orfeu, Cabrita, Eurico J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/104747
Resumo: FP7-SP3-People-606950 POCI-01-0145-FEDER-007728 Project No 022161
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spelling Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)GeneralSDG 3 - Good Health and Well-beingFP7-SP3-People-606950 POCI-01-0145-FEDER-007728 Project No 022161Alzheimer´s Disease (AD) is one of the most common neurodegenerative disorders worldwide. Excess of β-amyloid (Aβ), a peptide with a high propensity to misfold and self-aggregate, is believed to be the major contributor to the observed neuronal degeneration and cognitive decline in AD. Here, we characterize the epitope of a novel anti-Aβ monoclonal antibody, the STAB-MAb, which has previously demonstrated picomolar affinities for both monomers (KD = 80 pM) and fibrils (KD = 130 pM) of Aβ(1–42) and has shown therapeutic efficacy in preclinical mouse models of AD. Our findings reveal a widespread epitope that embraces several key Aβ residues that have been previously described as important in the Aβ fibrillation process. Of note, STAB-MAb exhibits a stronger affinity for the N-terminus of Aβ and stabilizes an α-helix conformation in the central to N-terminal region of the peptide, in addition to disrupting a characteristic salt-bridge of a hairpin structure present in fibrils. The NMR derived epitope supports the observed results from ThT-monitored fluorescence and electron microscopy experiments, in which STAB-MAb was shown to inhibit the formation of aggregates and promote disruption of pre-formed fibrils. In combination with the published in vitro and in vivo assays, our study highlights STAB-MAb as a rare and versatile antibody with analytical, diagnostic and therapeutic efficacy.UCIBIO - Applied Molecular Biosciences UnitRUNPosado-Fernández, AdriánAfonso, Cláudia F.Dória, GonçaloFlores, OrfeuCabrita, Eurico J.2020-09-25T22:22:07Z2019-12-012019-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/104747eng2045-2322PURE: 18898965https://doi.org/10.1038/s41598-019-47626-2info: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:RCAAP2024-03-11T04:50:17Zoai:run.unl.pt:10362/104747Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:40:20.149435Repositório 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 Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
title Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
spellingShingle Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
Posado-Fernández, Adrián
General
SDG 3 - Good Health and Well-being
title_short Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
title_full Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
title_fullStr Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
title_full_unstemmed Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
title_sort Epitope Mapping by NMR of a Novel Anti-Aβ Antibody (STAB-MAb)
author Posado-Fernández, Adrián
author_facet Posado-Fernández, Adrián
Afonso, Cláudia F.
Dória, Gonçalo
Flores, Orfeu
Cabrita, Eurico J.
author_role author
author2 Afonso, Cláudia F.
Dória, Gonçalo
Flores, Orfeu
Cabrita, Eurico J.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
RUN
dc.contributor.author.fl_str_mv Posado-Fernández, Adrián
Afonso, Cláudia F.
Dória, Gonçalo
Flores, Orfeu
Cabrita, Eurico J.
dc.subject.por.fl_str_mv General
SDG 3 - Good Health and Well-being
topic General
SDG 3 - Good Health and Well-being
description FP7-SP3-People-606950 POCI-01-0145-FEDER-007728 Project No 022161
publishDate 2019
dc.date.none.fl_str_mv 2019-12-01
2019-12-01T00:00:00Z
2020-09-25T22:22:07Z
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/10362/104747
url http://hdl.handle.net/10362/104747
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
PURE: 18898965
https://doi.org/10.1038/s41598-019-47626-2
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.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
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