Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1007/s00726-020-02847-y http://hdl.handle.net/11449/200455 |
Resumo: | Increasing resistance in antibiotic and chemotherapeutic treatments has been pushing studies of design and evaluation of bioactive peptides. Designing relies on different approaches from minimalist sequences and endogenous peptides modifications to computational libraries. Evaluation relies on microbiological tests. Aiming a deeper understanding, we chose the octapeptide Jelleine-I (JI) for its selective and low toxicity profile, designed small modifications combining the substitutions of Phe by Trp and Lys/His by Arg and tested the antimicrobial and anticancer activity on melanoma cells. Biophysical methods identified environment-dependent modulation of aggregation, but critical aggregation concentrations of JI and analogs in buffer show that peptides start membrane interactions as monomers. The presence of model membranes increases or reduces the partial aggregation of peptides. Compared to JI, analog JIF2WR shows the lowest tendency to aggregation on bacterial model membranes. JI and analogs are lytic to model membranes. Their composition-dependent performance indicates preference for the higher charged anionic bilayers in line with their superior performance toward Staphylococcus aureus and Streptococcus pneumoniae. JIF2WR presented the higher partitioning, higher lytic activity and lower aggregated contents. Despite these increased membranolytic activities, JIF2WR exhibited comparable antimicrobial activity in relation to JI at the expenses of some loss in selectivity. We found that the substitution Phe/Trp (JIF2W) tends to decrease antimicrobial but to increase anticancer activity and aggregation on model membranes and the toxicity toward human cells. However, the concomitant substitution Lys/His by Arg (JIF2WR) modulates some of these tendencies, increasing both the antimicrobial and the anticancer activity while decreasing the aggregation tendency. |
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Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregationAggregationAntimicrobial and anticancer peptidesJelleine-IPeptide–membrane interactionsShort-chain peptidesZeta potentialIncreasing resistance in antibiotic and chemotherapeutic treatments has been pushing studies of design and evaluation of bioactive peptides. Designing relies on different approaches from minimalist sequences and endogenous peptides modifications to computational libraries. Evaluation relies on microbiological tests. Aiming a deeper understanding, we chose the octapeptide Jelleine-I (JI) for its selective and low toxicity profile, designed small modifications combining the substitutions of Phe by Trp and Lys/His by Arg and tested the antimicrobial and anticancer activity on melanoma cells. Biophysical methods identified environment-dependent modulation of aggregation, but critical aggregation concentrations of JI and analogs in buffer show that peptides start membrane interactions as monomers. The presence of model membranes increases or reduces the partial aggregation of peptides. Compared to JI, analog JIF2WR shows the lowest tendency to aggregation on bacterial model membranes. JI and analogs are lytic to model membranes. Their composition-dependent performance indicates preference for the higher charged anionic bilayers in line with their superior performance toward Staphylococcus aureus and Streptococcus pneumoniae. JIF2WR presented the higher partitioning, higher lytic activity and lower aggregated contents. Despite these increased membranolytic activities, JIF2WR exhibited comparable antimicrobial activity in relation to JI at the expenses of some loss in selectivity. We found that the substitution Phe/Trp (JIF2W) tends to decrease antimicrobial but to increase anticancer activity and aggregation on model membranes and the toxicity toward human cells. However, the concomitant substitution Lys/His by Arg (JIF2WR) modulates some of these tendencies, increasing both the antimicrobial and the anticancer activity while decreasing the aggregation tendency.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Departamento de Física Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265Departamento de Química e Ciências Ambientais Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265Faceres Medical SchoolLaboratório de Neurobiologia Estrutural e Funcional (LaNEF) Departamento de Biofísica Universidade Federal de São Paulo R. Botucatu, 862, Edifício ECB, 7º andarCentro de Estudos de Insetos Sociais Universidade Estadual Paulista (Unesp), Câmpus Rio Claro, Av. 24-A, 1515Departamento de Doenças Dermatológicas Infecciosas e Parasitárias Faculdade de Medicina de São José do Rio PretoDepartamento de Física Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265Departamento de Química e Ciências Ambientais Universidade Estadual Paulista (Unesp) Instituto de Biociências Letras e Ciências Exatas (Ibilce), R. Cristóvão Colombo, 2265Centro de Estudos de Insetos Sociais Universidade Estadual Paulista (Unesp), Câmpus Rio Claro, Av. 24-A, 1515FAPESP: 2012/24259-0FAPESP: 2014/08372-7FAPESP: 2016/13368-4FAPESP: 2016/16212-5FAPESP: 2016/17951-6Universidade Estadual Paulista (Unesp)Faceres Medical SchoolUniversidade Federal de São Paulo (UNIFESP)Faculdade de Medicina de São José do Rio PretoMartins, Danubia Batista [UNESP]Pacca, Carolina Colombellida Silva, Annielle Mendes Britode Souza, Bibiana Monson [UNESP]de Almeida, Margarete Teresa GottardoPalma, Mario Sérgio [UNESP]Arcisio-Miranda, Manoeldos Santos Cabrera, Marcia Perez [UNESP]2020-12-12T02:07:06Z2020-12-12T02:07:06Z2020-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article725-741http://dx.doi.org/10.1007/s00726-020-02847-yAmino Acids, v. 52, n. 5, p. 725-741, 2020.1438-21990939-4451http://hdl.handle.net/11449/20045510.1007/s00726-020-02847-y2-s2.0-85085129285Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAmino Acidsinfo:eu-repo/semantics/openAccess2021-10-23T12:40:04Zoai:repositorio.unesp.br:11449/200455Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:48:59.906579Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
title |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
spellingShingle |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation Martins, Danubia Batista [UNESP] Aggregation Antimicrobial and anticancer peptides Jelleine-I Peptide–membrane interactions Short-chain peptides Zeta potential |
title_short |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
title_full |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
title_fullStr |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
title_full_unstemmed |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
title_sort |
Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation |
author |
Martins, Danubia Batista [UNESP] |
author_facet |
Martins, Danubia Batista [UNESP] Pacca, Carolina Colombelli da Silva, Annielle Mendes Brito de Souza, Bibiana Monson [UNESP] de Almeida, Margarete Teresa Gottardo Palma, Mario Sérgio [UNESP] Arcisio-Miranda, Manoel dos Santos Cabrera, Marcia Perez [UNESP] |
author_role |
author |
author2 |
Pacca, Carolina Colombelli da Silva, Annielle Mendes Brito de Souza, Bibiana Monson [UNESP] de Almeida, Margarete Teresa Gottardo Palma, Mario Sérgio [UNESP] Arcisio-Miranda, Manoel dos Santos Cabrera, Marcia Perez [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Faceres Medical School Universidade Federal de São Paulo (UNIFESP) Faculdade de Medicina de São José do Rio Preto |
dc.contributor.author.fl_str_mv |
Martins, Danubia Batista [UNESP] Pacca, Carolina Colombelli da Silva, Annielle Mendes Brito de Souza, Bibiana Monson [UNESP] de Almeida, Margarete Teresa Gottardo Palma, Mario Sérgio [UNESP] Arcisio-Miranda, Manoel dos Santos Cabrera, Marcia Perez [UNESP] |
dc.subject.por.fl_str_mv |
Aggregation Antimicrobial and anticancer peptides Jelleine-I Peptide–membrane interactions Short-chain peptides Zeta potential |
topic |
Aggregation Antimicrobial and anticancer peptides Jelleine-I Peptide–membrane interactions Short-chain peptides Zeta potential |
description |
Increasing resistance in antibiotic and chemotherapeutic treatments has been pushing studies of design and evaluation of bioactive peptides. Designing relies on different approaches from minimalist sequences and endogenous peptides modifications to computational libraries. Evaluation relies on microbiological tests. Aiming a deeper understanding, we chose the octapeptide Jelleine-I (JI) for its selective and low toxicity profile, designed small modifications combining the substitutions of Phe by Trp and Lys/His by Arg and tested the antimicrobial and anticancer activity on melanoma cells. Biophysical methods identified environment-dependent modulation of aggregation, but critical aggregation concentrations of JI and analogs in buffer show that peptides start membrane interactions as monomers. The presence of model membranes increases or reduces the partial aggregation of peptides. Compared to JI, analog JIF2WR shows the lowest tendency to aggregation on bacterial model membranes. JI and analogs are lytic to model membranes. Their composition-dependent performance indicates preference for the higher charged anionic bilayers in line with their superior performance toward Staphylococcus aureus and Streptococcus pneumoniae. JIF2WR presented the higher partitioning, higher lytic activity and lower aggregated contents. Despite these increased membranolytic activities, JIF2WR exhibited comparable antimicrobial activity in relation to JI at the expenses of some loss in selectivity. We found that the substitution Phe/Trp (JIF2W) tends to decrease antimicrobial but to increase anticancer activity and aggregation on model membranes and the toxicity toward human cells. However, the concomitant substitution Lys/His by Arg (JIF2WR) modulates some of these tendencies, increasing both the antimicrobial and the anticancer activity while decreasing the aggregation tendency. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-12T02:07:06Z 2020-12-12T02:07:06Z 2020-05-01 |
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/10.1007/s00726-020-02847-y Amino Acids, v. 52, n. 5, p. 725-741, 2020. 1438-2199 0939-4451 http://hdl.handle.net/11449/200455 10.1007/s00726-020-02847-y 2-s2.0-85085129285 |
url |
http://dx.doi.org/10.1007/s00726-020-02847-y http://hdl.handle.net/11449/200455 |
identifier_str_mv |
Amino Acids, v. 52, n. 5, p. 725-741, 2020. 1438-2199 0939-4451 10.1007/s00726-020-02847-y 2-s2.0-85085129285 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Amino Acids |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
725-741 |
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_ |
1808128706304016384 |