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

The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere witha 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 andfunctional e...

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Autores principales: Marín, Gustavo Horacio, Murail, Samuel, Andrini, Laura Beatriz, García, Marcela Nilda, Loisel, Severine, Tuffery, Pierre, Rebollo, Angelita
Formato: Articulo
Lenguaje:Inglés
Publicado: 2023
Materias:
Ciencias Médicas
peptide
cancer
breast
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/159988
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SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-159988
record_format dspace
spelling I19-R120-10915-1599882023-11-09T20:07:14Z http://sedici.unlp.edu.ar/handle/10915/159988 In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer Marín, Gustavo Horacio Murail, Samuel Andrini, Laura Beatriz García, Marcela Nilda Loisel, Severine Tuffery, Pierre Rebollo, Angelita 2023-04-03 2023-11-09T16:37:33Z en Ciencias Médicas peptide cancer breast The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere witha 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 andfunctional 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-theart 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 Facultad de Ciencias Médicas Articulo Articulo http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
peptide
cancer
breast
spellingShingle Ciencias Médicas
peptide
cancer
breast
Marín, Gustavo Horacio
Murail, Samuel
Andrini, Laura Beatriz
García, Marcela Nilda
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
topic_facet Ciencias Médicas
peptide
cancer
breast
description The combination of a tumor-penetrating peptide (TPP) with a peptide able to interfere witha 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 andfunctional 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-theart 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
format Articulo
Articulo
author Marín, Gustavo Horacio
Murail, Samuel
Andrini, Laura Beatriz
García, Marcela Nilda
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
author_facet Marín, Gustavo Horacio
Murail, Samuel
Andrini, Laura Beatriz
García, Marcela Nilda
Loisel, Severine
Tuffery, Pierre
Rebollo, Angelita
author_sort Marín, Gustavo Horacio
title In Silico and In Vivo Studies of a Tumor-Penetrating and Interfering Peptide with Antitumoral Effect on Xenograft Models of Breast Cancer
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
publishDate 2023
url http://sedici.unlp.edu.ar/handle/10915/159988
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