Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation

Detalhes bibliográficos
Autor(a) principal: Martins, Danubia Batista [UNESP]
Data de Publicação: 2020
Outros Autores: 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]
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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spelling 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
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