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In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs
Antimicrobial peptides are an important class of therapeutic agent used against a wide range of pathogens such as Gram-negative and Gram-positive bacteria, fungi, and viruses. Mastoparan (MpVT) is an α-helix and amphipathic tetradecapeptide obtained from Vespa tropica venom. This peptide exhibits an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779355/ https://www.ncbi.nlm.nih.gov/pubmed/35056876 http://dx.doi.org/10.3390/molecules27020561 |
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author | Rungsa, Prapenpuksiri Peigneur, Steve Jangpromma, Nisachon Klaynongsruang, Sompong Tytgat, Jan Daduang, Sakda |
author_facet | Rungsa, Prapenpuksiri Peigneur, Steve Jangpromma, Nisachon Klaynongsruang, Sompong Tytgat, Jan Daduang, Sakda |
author_sort | Rungsa, Prapenpuksiri |
collection | PubMed |
description | Antimicrobial peptides are an important class of therapeutic agent used against a wide range of pathogens such as Gram-negative and Gram-positive bacteria, fungi, and viruses. Mastoparan (MpVT) is an α-helix and amphipathic tetradecapeptide obtained from Vespa tropica venom. This peptide exhibits antibacterial activity. In this work, we investigate the effect of amino acid substitutions and deletion of the first three C-terminal residues on the structure–activity relationship. In this in silico study, the predicted structure of MpVT and its analog have characteristic features of linear cationic peptides rich in hydrophobic and basic amino acids without disulfide bonds. The secondary structure and the biological activity of six designed analogs are studied. The biological activity assays show that the substitution of phenylalanine (MpVT1) results in a higher antibacterial activity than that of MpVT without increasing toxicity. The analogs with the first three deleted C-terminal residues showed decreased antibacterial and hemolytic activity. The CD (circular dichroism) spectra of these peptides show a high content α-helical conformation in the presence of 40% 2,2,2-trifluoroethanol (TFE). In conclusion, the first three C-terminal deletions reduced the length of the α-helix, explaining the decreased biological activity. MpVTs show that the hemolytic activity of mastoparan is correlated to mean hydrophobicity and mean hydrophobic moment. The position and spatial arrangement of specific hydrophobic residues on the non-polar face of α-helical AMPs may be crucial for the interaction of AMPs with cell membranes. |
format | Online Article Text |
id | pubmed-8779355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87793552022-01-22 In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs Rungsa, Prapenpuksiri Peigneur, Steve Jangpromma, Nisachon Klaynongsruang, Sompong Tytgat, Jan Daduang, Sakda Molecules Article Antimicrobial peptides are an important class of therapeutic agent used against a wide range of pathogens such as Gram-negative and Gram-positive bacteria, fungi, and viruses. Mastoparan (MpVT) is an α-helix and amphipathic tetradecapeptide obtained from Vespa tropica venom. This peptide exhibits antibacterial activity. In this work, we investigate the effect of amino acid substitutions and deletion of the first three C-terminal residues on the structure–activity relationship. In this in silico study, the predicted structure of MpVT and its analog have characteristic features of linear cationic peptides rich in hydrophobic and basic amino acids without disulfide bonds. The secondary structure and the biological activity of six designed analogs are studied. The biological activity assays show that the substitution of phenylalanine (MpVT1) results in a higher antibacterial activity than that of MpVT without increasing toxicity. The analogs with the first three deleted C-terminal residues showed decreased antibacterial and hemolytic activity. The CD (circular dichroism) spectra of these peptides show a high content α-helical conformation in the presence of 40% 2,2,2-trifluoroethanol (TFE). In conclusion, the first three C-terminal deletions reduced the length of the α-helix, explaining the decreased biological activity. MpVTs show that the hemolytic activity of mastoparan is correlated to mean hydrophobicity and mean hydrophobic moment. The position and spatial arrangement of specific hydrophobic residues on the non-polar face of α-helical AMPs may be crucial for the interaction of AMPs with cell membranes. MDPI 2022-01-16 /pmc/articles/PMC8779355/ /pubmed/35056876 http://dx.doi.org/10.3390/molecules27020561 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 Rungsa, Prapenpuksiri Peigneur, Steve Jangpromma, Nisachon Klaynongsruang, Sompong Tytgat, Jan Daduang, Sakda In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title | In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title_full | In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title_fullStr | In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title_full_unstemmed | In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title_short | In Silico and In Vitro Structure–Activity Relationship of Mastoparan and Its Analogs |
title_sort | in silico and in vitro structure–activity relationship of mastoparan and its analogs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779355/ https://www.ncbi.nlm.nih.gov/pubmed/35056876 http://dx.doi.org/10.3390/molecules27020561 |
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