A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/82150 |
Resumo: | Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78. |
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A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial CellsMedicina básicaBasic medicineAntimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78.20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/82150eng1543-838410.1021/acs.molpharmaceut.5b00113Claudia MonteiroMarina PinheiroMariana FernandesSilvia MaiaCatarina L SeabraFrederico Ferreira da SilvaSalette ReisPaula GomesCristina C L Martinsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T15:39:04Zoai:repositorio-aberto.up.pt:10216/82150Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:28:46.212364Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
title |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
spellingShingle |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells Claudia Monteiro Medicina básica Basic medicine |
title_short |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
title_full |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
title_fullStr |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
title_full_unstemmed |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
title_sort |
A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells |
author |
Claudia Monteiro |
author_facet |
Claudia Monteiro Marina Pinheiro Mariana Fernandes Silvia Maia Catarina L Seabra Frederico Ferreira da Silva Salette Reis Paula Gomes Cristina C L Martins |
author_role |
author |
author2 |
Marina Pinheiro Mariana Fernandes Silvia Maia Catarina L Seabra Frederico Ferreira da Silva Salette Reis Paula Gomes Cristina C L Martins |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Claudia Monteiro Marina Pinheiro Mariana Fernandes Silvia Maia Catarina L Seabra Frederico Ferreira da Silva Salette Reis Paula Gomes Cristina C L Martins |
dc.subject.por.fl_str_mv |
Medicina básica Basic medicine |
topic |
Medicina básica Basic medicine |
description |
Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N- and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4-20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for MSI-78(4-20) based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2015-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/82150 |
url |
https://hdl.handle.net/10216/82150 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1543-8384 10.1021/acs.molpharmaceut.5b00113 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136199146733568 |