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Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein

Recent studies have shown that the peptide [des-Cys(11),Lys(12),Lys(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral...

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Autores principales: Bitencourt, Natália Vitória, Righetto, Gabriela Marinho, Camargo, Ilana Lopes Baratella Cunha, de Godoy, Mariana Ortiz, Guido, Rafael Victorio Carvalho, Oliva, Glaucius, Santos-Filho, Norival Alves, Cilli, Eduardo Maffud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964244/
https://www.ncbi.nlm.nih.gov/pubmed/36839758
http://dx.doi.org/10.3390/pharmaceutics15020436
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author Bitencourt, Natália Vitória
Righetto, Gabriela Marinho
Camargo, Ilana Lopes Baratella Cunha
de Godoy, Mariana Ortiz
Guido, Rafael Victorio Carvalho
Oliva, Glaucius
Santos-Filho, Norival Alves
Cilli, Eduardo Maffud
author_facet Bitencourt, Natália Vitória
Righetto, Gabriela Marinho
Camargo, Ilana Lopes Baratella Cunha
de Godoy, Mariana Ortiz
Guido, Rafael Victorio Carvalho
Oliva, Glaucius
Santos-Filho, Norival Alves
Cilli, Eduardo Maffud
author_sort Bitencourt, Natália Vitória
collection PubMed
description Recent studies have shown that the peptide [des-Cys(11),Lys(12),Lys(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PL(pro) enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PL(pro). The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PL(pro) of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns.
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spelling pubmed-99642442023-02-26 Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein Bitencourt, Natália Vitória Righetto, Gabriela Marinho Camargo, Ilana Lopes Baratella Cunha de Godoy, Mariana Ortiz Guido, Rafael Victorio Carvalho Oliva, Glaucius Santos-Filho, Norival Alves Cilli, Eduardo Maffud Pharmaceutics Article Recent studies have shown that the peptide [des-Cys(11),Lys(12),Lys(13)-(p-BthTX-I)(2)K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PL(pro) enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PL(pro). The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PL(pro) of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns. MDPI 2023-01-28 /pmc/articles/PMC9964244/ /pubmed/36839758 http://dx.doi.org/10.3390/pharmaceutics15020436 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
Bitencourt, Natália Vitória
Righetto, Gabriela Marinho
Camargo, Ilana Lopes Baratella Cunha
de Godoy, Mariana Ortiz
Guido, Rafael Victorio Carvalho
Oliva, Glaucius
Santos-Filho, Norival Alves
Cilli, Eduardo Maffud
Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title_full Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title_fullStr Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title_full_unstemmed Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title_short Effects of Dimerization, Dendrimerization, and Chirality in p-BthTX-I Peptide Analogs on the Antibacterial Activity and Enzymatic Inhibition of the SARS-CoV-2 PL(pro) Protein
title_sort effects of dimerization, dendrimerization, and chirality in p-bthtx-i peptide analogs on the antibacterial activity and enzymatic inhibition of the sars-cov-2 pl(pro) protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964244/
https://www.ncbi.nlm.nih.gov/pubmed/36839758
http://dx.doi.org/10.3390/pharmaceutics15020436
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