Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species
Érica de Oliveira Mello, Gabriel Bonan Taveira, André de Oliveira Carvalho, Valdirene Moreira Gomes Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadualdo Norte Fluminense Darcy R...
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Dove Medical Press
2019
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oai:doaj.org-article:e4981123559f42719e081d1e0b06268e2021-12-02T05:52:47ZImproved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species1178-2013https://doaj.org/article/e4981123559f42719e081d1e0b06268e2019-01-01T00:00:00Zhttps://www.dovepress.com/improved-smallest-peptides-based-on-positive-charge-increase-of-the-ga-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Érica de Oliveira Mello, Gabriel Bonan Taveira, André de Oliveira Carvalho, Valdirene Moreira Gomes Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadualdo Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro, Brazil Background: Plant defensins have a hallmark γ-core motif (GXCX3-9C) that is related to their antimicrobial properties. The aim of this work was to design synthetic peptides based on the region corresponding to the PνD1 defensin γ-core that are the smallest amino acid sequences that bear the strongest biological activity. Methods: We made rational substitutions of negatively charged amino acid residues with positively charged ones, and the reduction in length in the selected PνD1 γ-core sequence to verify whether the increased net positive charges and shortened length are related to the increase in antifungal activity. Herein, we opted to evaluate the action mechanism of γ33-41PνD1++ peptide due to its significant inhibitory effect on tested yeasts. In addition, it is the smallest construct comprising only nine amino acid residues, giving it a better possibility to be a prototype for designing a new antifungal drug, with lower costs to the pharmaceutical industry while still maintaining the strongest antimicrobial properties. Results: The γ33-41PνD1++ peptide caused the most toxic effects in the yeast Candida buinensis, leading to membrane permeabilization, viability loss, endogenous reactive oxygen species increase, the activation of metacaspase, and the loss of mitochondrial functionality, suggesting that this peptide triggers cell death via apoptosis. Conclusion: We observed that the antifungal activity of PνD1 is not strictly localized in the structural domain, which comprises the γ-core region and that the increase in the net positive charge is directly related to the increase in antifungal activity. Keywords: defensin, antimicrobial peptide, cationic, mechanism of actionMello ÉOTaveira GBde Oliveira Carvalho AGomes VMDove Medical Pressarticlesynthetic peptideantimicrobial peptidenet positive chargemechanism of actionMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 407-420 (2019) |
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synthetic peptide antimicrobial peptide net positive charge mechanism of action Medicine (General) R5-920 |
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synthetic peptide antimicrobial peptide net positive charge mechanism of action Medicine (General) R5-920 Mello ÉO Taveira GB de Oliveira Carvalho A Gomes VM Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| description |
Érica de Oliveira Mello, Gabriel Bonan Taveira, André de Oliveira Carvalho, Valdirene Moreira Gomes Laboratório de Fisiologia e Bioquímica de Microrganismos, Centro de Biociências e Biotecnologia, Universidade Estadualdo Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Rio de Janeiro, Brazil Background: Plant defensins have a hallmark γ-core motif (GXCX3-9C) that is related to their antimicrobial properties. The aim of this work was to design synthetic peptides based on the region corresponding to the PνD1 defensin γ-core that are the smallest amino acid sequences that bear the strongest biological activity. Methods: We made rational substitutions of negatively charged amino acid residues with positively charged ones, and the reduction in length in the selected PνD1 γ-core sequence to verify whether the increased net positive charges and shortened length are related to the increase in antifungal activity. Herein, we opted to evaluate the action mechanism of γ33-41PνD1++ peptide due to its significant inhibitory effect on tested yeasts. In addition, it is the smallest construct comprising only nine amino acid residues, giving it a better possibility to be a prototype for designing a new antifungal drug, with lower costs to the pharmaceutical industry while still maintaining the strongest antimicrobial properties. Results: The γ33-41PνD1++ peptide caused the most toxic effects in the yeast Candida buinensis, leading to membrane permeabilization, viability loss, endogenous reactive oxygen species increase, the activation of metacaspase, and the loss of mitochondrial functionality, suggesting that this peptide triggers cell death via apoptosis. Conclusion: We observed that the antifungal activity of PνD1 is not strictly localized in the structural domain, which comprises the γ-core region and that the increase in the net positive charge is directly related to the increase in antifungal activity. Keywords: defensin, antimicrobial peptide, cationic, mechanism of action |
| format |
article |
| author |
Mello ÉO Taveira GB de Oliveira Carvalho A Gomes VM |
| author_facet |
Mello ÉO Taveira GB de Oliveira Carvalho A Gomes VM |
| author_sort |
Mello ÉO |
| title |
Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| title_short |
Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| title_full |
Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| title_fullStr |
Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| title_full_unstemmed |
Improved smallest peptides based on positive charge increase of the γ-core motif from PνD1 and their mechanism of action against Candida species |
| title_sort |
improved smallest peptides based on positive charge increase of the γ-core motif from pνd1 and their mechanism of action against candida species |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/e4981123559f42719e081d1e0b06268e |
| work_keys_str_mv |
AT melloeo improvedsmallestpeptidesbasedonpositivechargeincreaseofthegammacoremotiffrompnud1andtheirmechanismofactionagainstcandidaspecies AT taveiragb improvedsmallestpeptidesbasedonpositivechargeincreaseofthegammacoremotiffrompnud1andtheirmechanismofactionagainstcandidaspecies AT deoliveiracarvalhoa improvedsmallestpeptidesbasedonpositivechargeincreaseofthegammacoremotiffrompnud1andtheirmechanismofactionagainstcandidaspecies AT gomesvm improvedsmallestpeptidesbasedonpositivechargeincreaseofthegammacoremotiffrompnud1andtheirmechanismofactionagainstcandidaspecies |
| _version_ |
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