Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides

Autores
Sanchis, Ivan; Spinelli, Roque; Dias, Jose; Brazzolotto, Xavier; Rietmann, Álvaro José; Aimaretti, Florencia Maria; Siano, Alvaro Sebastían
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced β-amyloid peptide (Aβ) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH2) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC50 value against hAChE reported for a peptide (0.99±0.02 μM) and inhibited 94.2 %±1.2 of AChE-induced Aβ aggregation at 10 μM. Furthermore, it inhibited hBChE (IC50, 15.44±0.91 μM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe2+ chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.
Fil: Sanchis, Ivan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Dias, Jose. Institut de Recherche Biomédicale des Armées; Francia
Fil: Brazzolotto, Xavier. Institut de Recherche Biomédicale des Armées; Francia
Fil: Rietmann, Álvaro José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Aimaretti, Florencia Maria. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Materia
ALZHEIMER'S DISEASE
AMYLOID BETA-PEPTIDES
CHOLINESTERASE INHIBITORS
PEPTIDES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/222703
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/222703
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed PeptidesSanchis, IvanSpinelli, RoqueDias, JoseBrazzolotto, XavierRietmann, Álvaro JoséAimaretti, Florencia MariaSiano, Alvaro SebastíanALZHEIMER'S DISEASEAMYLOID BETA-PEPTIDESCHOLINESTERASE INHIBITORSPEPTIDEShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced β-amyloid peptide (Aβ) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH2) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC50 value against hAChE reported for a peptide (0.99±0.02 μM) and inhibited 94.2 %±1.2 of AChE-induced Aβ aggregation at 10 μM. Furthermore, it inhibited hBChE (IC50, 15.44±0.91 μM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe2+ chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.Fil: Sanchis, Ivan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Dias, Jose. Institut de Recherche Biomédicale des Armées; FranciaFil: Brazzolotto, Xavier. Institut de Recherche Biomédicale des Armées; FranciaFil: Rietmann, Álvaro José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; ArgentinaFil: Aimaretti, Florencia Maria. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaWiley VCH Verlag2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/222703Sanchis, Ivan; Spinelli, Roque; Dias, Jose; Brazzolotto, Xavier; Rietmann, Álvaro José; et al.; Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides; Wiley VCH Verlag; Chemmedchem; 18; 12; 3-2023; 1-101860-7179CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202200691info:eu-repo/semantics/altIdentifier/doi/10.1002/cmdc.202200691info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:36Zoai:ri.conicet.gov.ar:11336/222703instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:07:36.926CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
title Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
spellingShingle Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
Sanchis, Ivan
ALZHEIMER'S DISEASE
AMYLOID BETA-PEPTIDES
CHOLINESTERASE INHIBITORS
PEPTIDES
title_short Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
title_full Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
title_fullStr Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
title_full_unstemmed Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
title_sort Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides
dc.creator.none.fl_str_mv Sanchis, Ivan
Spinelli, Roque
Dias, Jose
Brazzolotto, Xavier
Rietmann, Álvaro José
Aimaretti, Florencia Maria
Siano, Alvaro Sebastían
author Sanchis, Ivan
author_facet Sanchis, Ivan
Spinelli, Roque
Dias, Jose
Brazzolotto, Xavier
Rietmann, Álvaro José
Aimaretti, Florencia Maria
Siano, Alvaro Sebastían
author_role author
author2 Spinelli, Roque
Dias, Jose
Brazzolotto, Xavier
Rietmann, Álvaro José
Aimaretti, Florencia Maria
Siano, Alvaro Sebastían
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ALZHEIMER'S DISEASE
AMYLOID BETA-PEPTIDES
CHOLINESTERASE INHIBITORS
PEPTIDES
topic ALZHEIMER'S DISEASE
AMYLOID BETA-PEPTIDES
CHOLINESTERASE INHIBITORS
PEPTIDES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced β-amyloid peptide (Aβ) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH2) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC50 value against hAChE reported for a peptide (0.99±0.02 μM) and inhibited 94.2 %±1.2 of AChE-induced Aβ aggregation at 10 μM. Furthermore, it inhibited hBChE (IC50, 15.44±0.91 μM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe2+ chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.
Fil: Sanchis, Ivan. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Spinelli, Roque. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Dias, Jose. Institut de Recherche Biomédicale des Armées; Francia
Fil: Brazzolotto, Xavier. Institut de Recherche Biomédicale des Armées; Francia
Fil: Rietmann, Álvaro José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina
Fil: Aimaretti, Florencia Maria. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Química Organica. Laboratorio de Peptidos Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina
description The multifactorial nature of Alzheimer's disease (AD) is now widely recognized, which has increased the interest in compounds that can address more than one AD-associated targets. Herein, we report the inhibitory activity on the human cholinesterases (acetylcholinesterase, hAChE and butyrylcholinesterase, hBChE) and on the AChE-induced β-amyloid peptide (Aβ) aggregation by a series of peptide derivatives designed by mutating aliphatic residues for aromatic ones. We identified peptide W3 (LGWVSKGKLL-NH2) as an interesting scaffold for the development of new anti-AD multitarget-directed drugs. It showed the lowest IC50 value against hAChE reported for a peptide (0.99±0.02 μM) and inhibited 94.2 %±1.2 of AChE-induced Aβ aggregation at 10 μM. Furthermore, it inhibited hBChE (IC50, 15.44±0.91 μM), showed no in vivo toxicity in brine shrimp and had shown moderated radical scavenging and Fe2+ chelating capabilities in previous studies. The results are in line with multiple reports showing the utility of the indole moiety for the development of cholinesterase inhibitors.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/222703
Sanchis, Ivan; Spinelli, Roque; Dias, Jose; Brazzolotto, Xavier; Rietmann, Álvaro José; et al.; Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides; Wiley VCH Verlag; Chemmedchem; 18; 12; 3-2023; 1-10
1860-7179
CONICET Digital
CONICET
url http://hdl.handle.net/11336/222703
identifier_str_mv Sanchis, Ivan; Spinelli, Roque; Dias, Jose; Brazzolotto, Xavier; Rietmann, Álvaro José; et al.; Inhibition of Human Cholinesterases and in vitro β-Amyloid Aggregation by Rationally Designed Peptides; Wiley VCH Verlag; Chemmedchem; 18; 12; 3-2023; 1-10
1860-7179
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202200691
info:eu-repo/semantics/altIdentifier/doi/10.1002/cmdc.202200691
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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