In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer

Autores
Marin, Gustavo Horacio; Murail, Samuel; Andrini, Laura; Garcia, Marcela; Loisel, Severine; Tuffery, Pierre; Rebollo, Angelita
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein–peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer.
Fil: Marin, Gustavo Horacio. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Murail, Samuel. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Andrini, Laura. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Garcia, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Loisel, Severine. Université de Bretagne Occidentale; Francia
Fil: Tuffery, Pierre. Universite de Paris; Francia
Fil: Rebollo, Angelita. Universite Paris Sud. Faculte de Pharmacie; Francia
Materia
BREAST CANCER
PROTEIN–PROTEIN INTERACTION IN SILICO MODELING
TUMOR-PENETRATING PEPTIDE
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:11336/221771
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast CancerMarin, Gustavo HoracioMurail, SamuelAndrini, LauraGarcia, MarcelaLoisel, SeverineTuffery, PierreRebollo, AngelitaBREAST CANCERPROTEIN–PROTEIN INTERACTION IN SILICO MODELINGTUMOR-PENETRATING PEPTIDEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein–peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer.Fil: Marin, Gustavo Horacio. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Murail, Samuel. Universite de Paris; Francia. Centre National de la Recherche Scientifique; FranciaFil: Andrini, Laura. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Garcia, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; ArgentinaFil: Loisel, Severine. Université de Bretagne Occidentale; FranciaFil: Tuffery, Pierre. Universite de Paris; FranciaFil: Rebollo, Angelita. Universite Paris Sud. Faculte de Pharmacie; FranciaMultidisciplinary Digital Publishing Institute2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/221771Marin, Gustavo Horacio; Murail, Samuel; Andrini, Laura; Garcia, Marcela; Loisel, Severine; et al.; In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 1180; 4-2023; 1-161999-4923CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15041180info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/4/1180info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:52Zoai:ri.conicet.gov.ar:11336/221771instacron: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 09:51:52.545CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
title In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
spellingShingle In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
Marin, Gustavo Horacio
BREAST CANCER
PROTEIN–PROTEIN INTERACTION IN SILICO MODELING
TUMOR-PENETRATING PEPTIDE
title_short In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
title_full In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
title_fullStr In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
title_full_unstemmed In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
title_sort In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
dc.creator.none.fl_str_mv Marin, Gustavo Horacio
Murail, Samuel
Andrini, Laura
Garcia, Marcela
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
author Marin, Gustavo Horacio
author_facet Marin, Gustavo Horacio
Murail, Samuel
Andrini, Laura
Garcia, Marcela
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
author_role author
author2 Murail, Samuel
Andrini, Laura
Garcia, Marcela
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST CANCER
PROTEIN–PROTEIN INTERACTION IN SILICO MODELING
TUMOR-PENETRATING PEPTIDE
topic BREAST CANCER
PROTEIN–PROTEIN INTERACTION IN SILICO MODELING
TUMOR-PENETRATING PEPTIDE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein–peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer.
Fil: Marin, Gustavo Horacio. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Murail, Samuel. Universite de Paris; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Andrini, Laura. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Garcia, Marcela. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Cátedra de Histología y Embriología Animal; Argentina
Fil: Loisel, Severine. Université de Bretagne Occidentale; Francia
Fil: Tuffery, Pierre. Universite de Paris; Francia
Fil: Rebollo, Angelita. Universite Paris Sud. Faculte de Pharmacie; Francia
description The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere with a given protein–protein interaction (IP) is a promising strategy with potential clinical application. Little is known about the impact of fusing a TPP with an IP, both in terms of internalization and functional effect. Here, we analyze these aspects in the context of breast cancer, targeting PP2A/SET interaction, using both in silico and in vivo approaches. Our results support the fact that state-of-the-art deep learning approaches developed for protein–peptide interaction modeling can reliably identify good candidate poses for the IP-TPP in interaction with the Neuropilin-1 receptor. The association of the IP with the TPP does not seem to affect the ability of the TPP to bind to Neuropilin-1. Molecular simulation results suggest that peptide IP-GG-LinTT1 in a cleaved form interacts with Neuropilin-1 in a more stable manner and has a more helical secondary structure than the cleaved IP-GG-iRGD. Surprisingly, in silico investigations also suggest that the non-cleaved TPPs can bind the Neuropilin-1 in a stable manner. The in vivo results using xenografts models show that both bifunctional peptides resulting from the combination of the IP and either LinTT1 or iRGD are effective against tumoral growth. The peptide iRGD-IP shows the highest stability to serum proteases degradation while having the same antitumoral effect as Lin TT1-IP, which is more sensitive to proteases degradation. Our results support the development of the TPP-IP strategy as therapeutic peptides against cancer.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
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/11336/221771
Marin, Gustavo Horacio; Murail, Samuel; Andrini, Laura; Garcia, Marcela; Loisel, Severine; et al.; In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 1180; 4-2023; 1-16
1999-4923
CONICET Digital
CONICET
url http://hdl.handle.net/11336/221771
identifier_str_mv Marin, Gustavo Horacio; Murail, Samuel; Andrini, Laura; Garcia, Marcela; Loisel, Severine; et al.; In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer; Multidisciplinary Digital Publishing Institute; Pharmaceutics; 15; 1180; 4-2023; 1-16
1999-4923
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/pharmaceutics15041180
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1999-4923/15/4/1180
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 Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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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