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Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2

At the beginning of 2020, the pandemic caused by the SARS-CoV-2 virus led to the fast sequencing of its genome to facilitate molecular engineering strategies to control the pathogen’s spread. The spike (S) glycoprotein has been identified as the leading therapeutic agent due to its role in localizin...

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Autores principales: Henao, Maria C., Ocasion, Camila, Puentes, Paola Ruiz, González-Melo, Cristina, Quezada, Valentina, Cifuentes, Javier, Yepes, Arnovis, Burgos, Juan C., Cruz, Juan C., Reyes, Luis H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229458/
https://www.ncbi.nlm.nih.gov/pubmed/35736307
http://dx.doi.org/10.3390/membranes12060600
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author Henao, Maria C.
Ocasion, Camila
Puentes, Paola Ruiz
González-Melo, Cristina
Quezada, Valentina
Cifuentes, Javier
Yepes, Arnovis
Burgos, Juan C.
Cruz, Juan C.
Reyes, Luis H.
author_facet Henao, Maria C.
Ocasion, Camila
Puentes, Paola Ruiz
González-Melo, Cristina
Quezada, Valentina
Cifuentes, Javier
Yepes, Arnovis
Burgos, Juan C.
Cruz, Juan C.
Reyes, Luis H.
author_sort Henao, Maria C.
collection PubMed
description At the beginning of 2020, the pandemic caused by the SARS-CoV-2 virus led to the fast sequencing of its genome to facilitate molecular engineering strategies to control the pathogen’s spread. The spike (S) glycoprotein has been identified as the leading therapeutic agent due to its role in localizing the ACE2 receptor in the host’s pulmonary cell membrane, binding, and eventually infecting the cells. Due to the difficulty of delivering bioactive molecules to the intracellular space, we hypothesized that the S protein could serve as a source of membrane translocating peptides. AHB-1, AHB-2, and AHB-3 peptides were identified and analyzed on a membrane model of DPPC (dipalmitoylphosphatidylcholine) using molecular dynamics (MD) simulations. An umbrella sampling approach was used to quantify the energy barrier necessary to cross the boundary (13.2 to 34.9 kcal/mol), and a flat-bottom pulling helped to gain a deeper understanding of the membrane’s permeation dynamics. Our studies revealed that the novel peptide AHB-1 exhibited comparable penetration potential of already known potent cell-penetrating peptides (CPPs) such as TP2, Buforin II, and Frenatin 2.3s. Results were confirmed by in vitro analysis of the peptides conjugated to chitosan nanoparticles, demonstrating its ability to reach the cytosol and escape endosomes, while maintaining high biocompatibility levels according to standardized assays.
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spelling pubmed-92294582022-06-25 Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2 Henao, Maria C. Ocasion, Camila Puentes, Paola Ruiz González-Melo, Cristina Quezada, Valentina Cifuentes, Javier Yepes, Arnovis Burgos, Juan C. Cruz, Juan C. Reyes, Luis H. Membranes (Basel) Article At the beginning of 2020, the pandemic caused by the SARS-CoV-2 virus led to the fast sequencing of its genome to facilitate molecular engineering strategies to control the pathogen’s spread. The spike (S) glycoprotein has been identified as the leading therapeutic agent due to its role in localizing the ACE2 receptor in the host’s pulmonary cell membrane, binding, and eventually infecting the cells. Due to the difficulty of delivering bioactive molecules to the intracellular space, we hypothesized that the S protein could serve as a source of membrane translocating peptides. AHB-1, AHB-2, and AHB-3 peptides were identified and analyzed on a membrane model of DPPC (dipalmitoylphosphatidylcholine) using molecular dynamics (MD) simulations. An umbrella sampling approach was used to quantify the energy barrier necessary to cross the boundary (13.2 to 34.9 kcal/mol), and a flat-bottom pulling helped to gain a deeper understanding of the membrane’s permeation dynamics. Our studies revealed that the novel peptide AHB-1 exhibited comparable penetration potential of already known potent cell-penetrating peptides (CPPs) such as TP2, Buforin II, and Frenatin 2.3s. Results were confirmed by in vitro analysis of the peptides conjugated to chitosan nanoparticles, demonstrating its ability to reach the cytosol and escape endosomes, while maintaining high biocompatibility levels according to standardized assays. MDPI 2022-06-10 /pmc/articles/PMC9229458/ /pubmed/35736307 http://dx.doi.org/10.3390/membranes12060600 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Henao, Maria C.
Ocasion, Camila
Puentes, Paola Ruiz
González-Melo, Cristina
Quezada, Valentina
Cifuentes, Javier
Yepes, Arnovis
Burgos, Juan C.
Cruz, Juan C.
Reyes, Luis H.
Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title_full Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title_fullStr Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title_full_unstemmed Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title_short Translocating Peptides of Biomedical Interest Obtained from the Spike (S) Glycoprotein of the SARS-CoV-2
title_sort translocating peptides of biomedical interest obtained from the spike (s) glycoprotein of the sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229458/
https://www.ncbi.nlm.nih.gov/pubmed/35736307
http://dx.doi.org/10.3390/membranes12060600
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