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Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study
Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826669/ https://www.ncbi.nlm.nih.gov/pubmed/33445613 http://dx.doi.org/10.3390/ijms22020691 |
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author | Ramos-Martín, Francisco D’Amelio, Nicola |
author_facet | Ramos-Martín, Francisco D’Amelio, Nicola |
author_sort | Ramos-Martín, Francisco |
collection | PubMed |
description | Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity against most ESKAPE bacteria and fungi. Here, we present the first study of its mechanism of action based on molecular dynamics (MD) simulations and sequence-property alignment. Although unstructured in solution, predictions highlight the presence of two helices separated by a flexible hinge containing P24 and stabilized by the interaction of W2 with target biomembranes: an amphipathic helix-I and a poorly structured helix-II. Both MD and sequence-property alignment point to the important role of helix I in both the activity and the interaction with biomembranes. MD reveals that CXJ interacts mainly with phosphatidylserine (PS) but also with phosphatidylethanolamine (PE) headgroups, both found in the outer leaflet of cancer cells, while salt bridges with phosphate moieties are prevalent in bacterial biomimetic membranes composed of PE, phosphatidylglycerol (PG) and cardiolipin (CL). The antibacterial activity of CXJ might also explain its interaction with mitochondria, whose phospholipid composition recalls that of bacteria and its capability to induce apoptosis in cancer cells. |
format | Online Article Text |
id | pubmed-7826669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78266692021-01-25 Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study Ramos-Martín, Francisco D’Amelio, Nicola Int J Mol Sci Article Esophageal cancer is an aggressive lethal malignancy causing thousands of deaths every year. While current treatments have poor outcomes, cecropinXJ (CXJ) is one of the very few peptides with demonstrated in vivo activity. The great interest in CXJ stems from its low toxicity and additional activity against most ESKAPE bacteria and fungi. Here, we present the first study of its mechanism of action based on molecular dynamics (MD) simulations and sequence-property alignment. Although unstructured in solution, predictions highlight the presence of two helices separated by a flexible hinge containing P24 and stabilized by the interaction of W2 with target biomembranes: an amphipathic helix-I and a poorly structured helix-II. Both MD and sequence-property alignment point to the important role of helix I in both the activity and the interaction with biomembranes. MD reveals that CXJ interacts mainly with phosphatidylserine (PS) but also with phosphatidylethanolamine (PE) headgroups, both found in the outer leaflet of cancer cells, while salt bridges with phosphate moieties are prevalent in bacterial biomimetic membranes composed of PE, phosphatidylglycerol (PG) and cardiolipin (CL). The antibacterial activity of CXJ might also explain its interaction with mitochondria, whose phospholipid composition recalls that of bacteria and its capability to induce apoptosis in cancer cells. MDPI 2021-01-12 /pmc/articles/PMC7826669/ /pubmed/33445613 http://dx.doi.org/10.3390/ijms22020691 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ramos-Martín, Francisco D’Amelio, Nicola Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title | Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title_full | Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title_fullStr | Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title_full_unstemmed | Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title_short | Molecular Basis of the Anticancer and Antibacterial Properties of CecropinXJ Peptide: An In Silico Study |
title_sort | molecular basis of the anticancer and antibacterial properties of cecropinxj peptide: an in silico study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826669/ https://www.ncbi.nlm.nih.gov/pubmed/33445613 http://dx.doi.org/10.3390/ijms22020691 |
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