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Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach
In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. Howe...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966382/ https://www.ncbi.nlm.nih.gov/pubmed/36839798 http://dx.doi.org/10.3390/pharmaceutics15020474 |
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author | Pereira, Alfredo Valdés-Muñoz, Elizabeth Marican, Adolfo Cabrera-Barjas, Gustavo Vijayakumar, Sekar Valdés, Oscar Rafael, Diana Andrade, Fernanda Abaca, Paulina Bustos, Daniel Durán-Lara, Esteban F. |
author_facet | Pereira, Alfredo Valdés-Muñoz, Elizabeth Marican, Adolfo Cabrera-Barjas, Gustavo Vijayakumar, Sekar Valdés, Oscar Rafael, Diana Andrade, Fernanda Abaca, Paulina Bustos, Daniel Durán-Lara, Esteban F. |
author_sort | Pereira, Alfredo |
collection | PubMed |
description | In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP. |
format | Online Article Text |
id | pubmed-9966382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99663822023-02-26 Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach Pereira, Alfredo Valdés-Muñoz, Elizabeth Marican, Adolfo Cabrera-Barjas, Gustavo Vijayakumar, Sekar Valdés, Oscar Rafael, Diana Andrade, Fernanda Abaca, Paulina Bustos, Daniel Durán-Lara, Esteban F. Pharmaceutics Article In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP. MDPI 2023-01-31 /pmc/articles/PMC9966382/ /pubmed/36839798 http://dx.doi.org/10.3390/pharmaceutics15020474 Text en © 2023 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 Pereira, Alfredo Valdés-Muñoz, Elizabeth Marican, Adolfo Cabrera-Barjas, Gustavo Vijayakumar, Sekar Valdés, Oscar Rafael, Diana Andrade, Fernanda Abaca, Paulina Bustos, Daniel Durán-Lara, Esteban F. Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title | Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title_full | Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title_fullStr | Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title_full_unstemmed | Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title_short | Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach |
title_sort | rational design of hydrogels for cationic antimicrobial peptide delivery: a molecular modeling approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966382/ https://www.ncbi.nlm.nih.gov/pubmed/36839798 http://dx.doi.org/10.3390/pharmaceutics15020474 |
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