Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1002/pep2.24243 http://hdl.handle.net/11449/233532 |
Resumo: | The peptide (p-BthTX-I)2 [(KKYRYHLKPFCKK)2] and its analog des-Lys12,Lys13-(p-BthTX-I)2 [(KKYRYHLKPFC)2] showed activity against bacteria and potential specificity against prokaryotic cells. In this study, we synthesized the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K [(KKYRYHLKPF)2K] with a Lys instead of a Cys residue in the dimerization step, beginning the SPPS with Fmoc-Lys(Fmoc)-OH. This change avoided Cys oxidation, decreasing one step in the original peptide synthesis and obtaining a smaller and more stable peptide. The antimicrobial activity of the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K was superior to that of the (p-BthTX-I)2 peptide against the bacterial strains tested. Additionally, to evaluate the impact of the linker position on peptide dimerization, we synthesized peptide E(p-BthTX-I)2 [E(KKYRYHLKPFCKK)2] using Fmoc-Glu-OH at the end of the synthesis. This N-terminal dimeric peptide did not increase the antibacterial activity, indicating that the free N-terminal is essential for (p-BthTX-I)2 activity. Additionally, we observed lower antimicrobial activity by substituting positive and aromatic residues with Ala in the alanine scanning assay, irrespective of the amino acid change, indicating that each amino acid is essential for the mechanism of action of the peptide. Therefore, we demonstrated that the (p-BthTX-I)2 analog, which is shorter and synthesized by an easier process leading to a more stable peptide, is the most antibacterial active peptide against multidrug-resistant bacteria and does not increase hemolysis activity. |
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Repositório Institucional da UNESP |
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spelling |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I(p-BthTX-I)2Ala scanantimicrobial peptidesmultidrug-resistant bacteriap-BthTX-IThe peptide (p-BthTX-I)2 [(KKYRYHLKPFCKK)2] and its analog des-Lys12,Lys13-(p-BthTX-I)2 [(KKYRYHLKPFC)2] showed activity against bacteria and potential specificity against prokaryotic cells. In this study, we synthesized the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K [(KKYRYHLKPF)2K] with a Lys instead of a Cys residue in the dimerization step, beginning the SPPS with Fmoc-Lys(Fmoc)-OH. This change avoided Cys oxidation, decreasing one step in the original peptide synthesis and obtaining a smaller and more stable peptide. The antimicrobial activity of the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K was superior to that of the (p-BthTX-I)2 peptide against the bacterial strains tested. Additionally, to evaluate the impact of the linker position on peptide dimerization, we synthesized peptide E(p-BthTX-I)2 [E(KKYRYHLKPFCKK)2] using Fmoc-Glu-OH at the end of the synthesis. This N-terminal dimeric peptide did not increase the antibacterial activity, indicating that the free N-terminal is essential for (p-BthTX-I)2 activity. Additionally, we observed lower antimicrobial activity by substituting positive and aromatic residues with Ala in the alanine scanning assay, irrespective of the amino acid change, indicating that each amino acid is essential for the mechanism of action of the peptide. Therefore, we demonstrated that the (p-BthTX-I)2 analog, which is shorter and synthesized by an easier process leading to a more stable peptide, is the most antibacterial active peptide against multidrug-resistant bacteria and does not increase hemolysis activity.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto de Química UNESPInstituto de Física de São Carlos USP, São CarlosInstituto de Química UNESPFAPESP: 2012/15346-7FAPESP: 2013/07600-3FAPESP: 2014/05538-1Universidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Santos-Filho, Norival Alves [UNESP]Righetto, Gabriela MarinhoPereira, Marina Rodrigues [UNESP]Piccoli, Julia Pinto [UNESP]Almeida, Larissa Mathias Teizen [UNESP]Leal, Thainá Cristina [UNESP]Camargo, Ilana Lopes Baratella CunhaCilli, Eduardo Maffud [UNESP]2022-05-01T09:00:57Z2022-05-01T09:00:57Z2022-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1002/pep2.24243Peptide Science, v. 114, n. 2, 2022.2475-8817http://hdl.handle.net/11449/23353210.1002/pep2.242432-s2.0-85114903212Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPeptide Scienceinfo:eu-repo/semantics/openAccess2022-05-01T09:00:57Zoai:repositorio.unesp.br:11449/233532Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-05-01T09:00:57Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
title |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
spellingShingle |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I Santos-Filho, Norival Alves [UNESP] (p-BthTX-I)2 Ala scan antimicrobial peptides multidrug-resistant bacteria p-BthTX-I |
title_short |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
title_full |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
title_fullStr |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
title_full_unstemmed |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
title_sort |
Effect of C-terminal and N-terminal dimerization and alanine scanning on antibacterial activity of the analogs of the peptide p-BthTX-I |
author |
Santos-Filho, Norival Alves [UNESP] |
author_facet |
Santos-Filho, Norival Alves [UNESP] Righetto, Gabriela Marinho Pereira, Marina Rodrigues [UNESP] Piccoli, Julia Pinto [UNESP] Almeida, Larissa Mathias Teizen [UNESP] Leal, Thainá Cristina [UNESP] Camargo, Ilana Lopes Baratella Cunha Cilli, Eduardo Maffud [UNESP] |
author_role |
author |
author2 |
Righetto, Gabriela Marinho Pereira, Marina Rodrigues [UNESP] Piccoli, Julia Pinto [UNESP] Almeida, Larissa Mathias Teizen [UNESP] Leal, Thainá Cristina [UNESP] Camargo, Ilana Lopes Baratella Cunha Cilli, Eduardo Maffud [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Santos-Filho, Norival Alves [UNESP] Righetto, Gabriela Marinho Pereira, Marina Rodrigues [UNESP] Piccoli, Julia Pinto [UNESP] Almeida, Larissa Mathias Teizen [UNESP] Leal, Thainá Cristina [UNESP] Camargo, Ilana Lopes Baratella Cunha Cilli, Eduardo Maffud [UNESP] |
dc.subject.por.fl_str_mv |
(p-BthTX-I)2 Ala scan antimicrobial peptides multidrug-resistant bacteria p-BthTX-I |
topic |
(p-BthTX-I)2 Ala scan antimicrobial peptides multidrug-resistant bacteria p-BthTX-I |
description |
The peptide (p-BthTX-I)2 [(KKYRYHLKPFCKK)2] and its analog des-Lys12,Lys13-(p-BthTX-I)2 [(KKYRYHLKPFC)2] showed activity against bacteria and potential specificity against prokaryotic cells. In this study, we synthesized the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K [(KKYRYHLKPF)2K] with a Lys instead of a Cys residue in the dimerization step, beginning the SPPS with Fmoc-Lys(Fmoc)-OH. This change avoided Cys oxidation, decreasing one step in the original peptide synthesis and obtaining a smaller and more stable peptide. The antimicrobial activity of the peptide des-Cys11,Lys12,Lys13-(p-BthTX-I)2K was superior to that of the (p-BthTX-I)2 peptide against the bacterial strains tested. Additionally, to evaluate the impact of the linker position on peptide dimerization, we synthesized peptide E(p-BthTX-I)2 [E(KKYRYHLKPFCKK)2] using Fmoc-Glu-OH at the end of the synthesis. This N-terminal dimeric peptide did not increase the antibacterial activity, indicating that the free N-terminal is essential for (p-BthTX-I)2 activity. Additionally, we observed lower antimicrobial activity by substituting positive and aromatic residues with Ala in the alanine scanning assay, irrespective of the amino acid change, indicating that each amino acid is essential for the mechanism of action of the peptide. Therefore, we demonstrated that the (p-BthTX-I)2 analog, which is shorter and synthesized by an easier process leading to a more stable peptide, is the most antibacterial active peptide against multidrug-resistant bacteria and does not increase hemolysis activity. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05-01T09:00:57Z 2022-05-01T09:00:57Z 2022-03-01 |
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 |
http://dx.doi.org/10.1002/pep2.24243 Peptide Science, v. 114, n. 2, 2022. 2475-8817 http://hdl.handle.net/11449/233532 10.1002/pep2.24243 2-s2.0-85114903212 |
url |
http://dx.doi.org/10.1002/pep2.24243 http://hdl.handle.net/11449/233532 |
identifier_str_mv |
Peptide Science, v. 114, n. 2, 2022. 2475-8817 10.1002/pep2.24243 2-s2.0-85114903212 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Peptide Science |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799964965580308480 |