Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552

Autores
Astrada, Soledad; Gomez, Yolanda; Barrera Guisasola, Exequiel Ernesto; Obal, Gonzalo; Pritsch, Otto; Pantano, Sergio; Vallespí, Maribel G.; Bollati Fogolín, Mariela
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein–peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite–COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.
Fil: Astrada, Soledad. Instituto Pasteur de Montevideo; Uruguay
Fil: Gomez, Yolanda. Center For Genetic Engineering And Biotechnology; Cuba
Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Pasteur de Montevideo. Laboratorio de Simuladores Biomoleculares; Uruguay
Fil: Obal, Gonzalo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Pritsch, Otto. Instituto Pasteur de Montevideo; Uruguay
Fil: Pantano, Sergio. Instituto Pasteur de Montevideo; Uruguay
Fil: Vallespí, Maribel G.. Center For Genetic Engineering And Biotechnology; Cuba
Fil: Bollati Fogolín, Mariela. Instituto Pasteur de Montevideo; Uruguay
Materia
AMINO ACIDS
APOPTOSIS
CELL PENETRATING PEPTIDE
COMMD1
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:11336/90821
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/90821
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552Astrada, SoledadGomez, YolandaBarrera Guisasola, Exequiel ErnestoObal, GonzaloPritsch, OttoPantano, SergioVallespí, Maribel G.Bollati Fogolín, MarielaAMINO ACIDSAPOPTOSISCELL PENETRATING PEPTIDECOMMD1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein–peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite–COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.Fil: Astrada, Soledad. Instituto Pasteur de Montevideo; UruguayFil: Gomez, Yolanda. Center For Genetic Engineering And Biotechnology; CubaFil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Pasteur de Montevideo. Laboratorio de Simuladores Biomoleculares; UruguayFil: Obal, Gonzalo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Pritsch, Otto. Instituto Pasteur de Montevideo; UruguayFil: Pantano, Sergio. Instituto Pasteur de Montevideo; UruguayFil: Vallespí, Maribel G.. Center For Genetic Engineering And Biotechnology; CubaFil: Bollati Fogolín, Mariela. Instituto Pasteur de Montevideo; UruguayJohn Wiley & Sons Ltd2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/90821Astrada, Soledad; Gomez, Yolanda; Barrera Guisasola, Exequiel Ernesto; Obal, Gonzalo; Pritsch, Otto; et al.; Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552; John Wiley & Sons Ltd; Journal Of Peptide Science; 22; 11-12; 11-2016; 711-7221075-2617CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/psc.2934info:eu-repo/semantics/altIdentifier/doi/10.1002/psc.2934info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:16Zoai:ri.conicet.gov.ar:11336/90821instacron: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:34982025-09-29 09:33:16.909CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
title Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
spellingShingle Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
Astrada, Soledad
AMINO ACIDS
APOPTOSIS
CELL PENETRATING PEPTIDE
COMMD1
title_short Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
title_full Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
title_fullStr Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
title_full_unstemmed Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
title_sort Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552
dc.creator.none.fl_str_mv Astrada, Soledad
Gomez, Yolanda
Barrera Guisasola, Exequiel Ernesto
Obal, Gonzalo
Pritsch, Otto
Pantano, Sergio
Vallespí, Maribel G.
Bollati Fogolín, Mariela
author Astrada, Soledad
author_facet Astrada, Soledad
Gomez, Yolanda
Barrera Guisasola, Exequiel Ernesto
Obal, Gonzalo
Pritsch, Otto
Pantano, Sergio
Vallespí, Maribel G.
Bollati Fogolín, Mariela
author_role author
author2 Gomez, Yolanda
Barrera Guisasola, Exequiel Ernesto
Obal, Gonzalo
Pritsch, Otto
Pantano, Sergio
Vallespí, Maribel G.
Bollati Fogolín, Mariela
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMINO ACIDS
APOPTOSIS
CELL PENETRATING PEPTIDE
COMMD1
topic AMINO ACIDS
APOPTOSIS
CELL PENETRATING PEPTIDE
COMMD1
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein–peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite–COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.
Fil: Astrada, Soledad. Instituto Pasteur de Montevideo; Uruguay
Fil: Gomez, Yolanda. Center For Genetic Engineering And Biotechnology; Cuba
Fil: Barrera Guisasola, Exequiel Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Pasteur de Montevideo. Laboratorio de Simuladores Biomoleculares; Uruguay
Fil: Obal, Gonzalo. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Pritsch, Otto. Instituto Pasteur de Montevideo; Uruguay
Fil: Pantano, Sergio. Instituto Pasteur de Montevideo; Uruguay
Fil: Vallespí, Maribel G.. Center For Genetic Engineering And Biotechnology; Cuba
Fil: Bollati Fogolín, Mariela. Instituto Pasteur de Montevideo; Uruguay
description Because of resistance development by cancer cells against current anticancer drugs, there is a considerable interest in developing novel antitumor agents. We have previously demonstrated that CIGB-552, a novel cell-penetrating synthetic peptide, was effective in reducing tumor size and increasing lifespan in tumor-bearing mice. Studies of protein–peptide interactions have shown that COMMD1 protein is a major mediator of CIGB-552 antitumor activity. Furthermore, a typical serine-protease degradation pattern for CIGB-552 in BALB/c mice serum was identified, yielding peptides which differ from CIGB-552 in size and physical properties. In the present study, we show the results obtained from a comparative analysis between CIGB-552 and its main metabolites regarding physicochemical properties, cellular internalization, and their capability to elicit apoptosis in MCF-7 cells. None of the analyzed metabolites proved to be as effective as CIGB-552 in promoting apoptosis in MCF-7. Taking into account these results, it seemed important to examine their cell-penetrating capacity and interaction with COMMD1. We show that internalization, a lipid binding-dependent process, is impaired as well as metabolite–COMMD1 interaction, key component of the apoptotic mechanism. Altogether, our results suggest that features conferred by the amino acid sequence are decisive for CIGB-552 biological activity, turning it into the minimal functional unit.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
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/11336/90821
Astrada, Soledad; Gomez, Yolanda; Barrera Guisasola, Exequiel Ernesto; Obal, Gonzalo; Pritsch, Otto; et al.; Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552; John Wiley & Sons Ltd; Journal Of Peptide Science; 22; 11-12; 11-2016; 711-722
1075-2617
CONICET Digital
CONICET
url http://hdl.handle.net/11336/90821
identifier_str_mv Astrada, Soledad; Gomez, Yolanda; Barrera Guisasola, Exequiel Ernesto; Obal, Gonzalo; Pritsch, Otto; et al.; Comparative analysis reveals amino acids critical for anticancer activity of peptide CIGB-552; John Wiley & Sons Ltd; Journal Of Peptide Science; 22; 11-12; 11-2016; 711-722
1075-2617
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://onlinelibrary.wiley.com/doi/abs/10.1002/psc.2934
info:eu-repo/semantics/altIdentifier/doi/10.1002/psc.2934
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
dc.publisher.none.fl_str_mv John Wiley & Sons Ltd
publisher.none.fl_str_mv John Wiley & Sons Ltd
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 13.070432

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