Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/123456789/20011 |
Resumo: | The high incidence of nosocomial infection, along with the advents of bacterial resistance to multiple drugs has increased exponentially, making it necessary the search for new tools to control these pathogens. The present study focuses on the development of butylatus-1, -2 and -3, which were rationally designed based on a scorpion’s peptide from Tityus serrulatus, named TsAP-1, in order to increase the bactericidal activity with a decrease in cytotoxicity. The analogue peptides were obtained through the punctual modification of amino acid residues based in an amphipathic pattern HHh+H (h+ : positively charged hydrophilic amino acid residues; H: hydrophobic amino acid residues) found in the TsAP-1 parental peptide, thereby reducing hydrophobicity and increasing both hydrophobic moment and net charge. It was observed that the helical content also increased, promoting the increase in amphipacity of the analogue peptides Regarding their biological activities, it was observed that the parental peptide TsAP-1 did not present antibacterial activity at the maximal concentration range tested. In contrast, the analogues butylatus-1 and -2 were capable of inhibiting susceptible Escherichia coli and Enterococcus faecalis at 5.3 and 43.1 µM respectively. Interestingly, the antibacterial potential of the butylatus-3 analogue was selective to E. coli KpC, at 39.6 µM. In terms of hemolytic properties, only butylatus-2 presented cellular hemolysis at 43.1 µM. Despite the reported data on the good performance of analogues peptides, butylatus-1 stands out as an excellent candidate in the development of a new alternative against infections caused by pathogenic bacteria, due to the high action potential of at low dosages and not shown hemolysis. |
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Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus spAtividade microbianaPeptídeos antimicrobianosToxina de escorpiãoBiofísica computacionalMicrobian activityAntimicrobial peptideScorpion toxinComputational biophysicsCNPQ::CIENCIAS BIOLOGICASThe high incidence of nosocomial infection, along with the advents of bacterial resistance to multiple drugs has increased exponentially, making it necessary the search for new tools to control these pathogens. The present study focuses on the development of butylatus-1, -2 and -3, which were rationally designed based on a scorpion’s peptide from Tityus serrulatus, named TsAP-1, in order to increase the bactericidal activity with a decrease in cytotoxicity. The analogue peptides were obtained through the punctual modification of amino acid residues based in an amphipathic pattern HHh+H (h+ : positively charged hydrophilic amino acid residues; H: hydrophobic amino acid residues) found in the TsAP-1 parental peptide, thereby reducing hydrophobicity and increasing both hydrophobic moment and net charge. It was observed that the helical content also increased, promoting the increase in amphipacity of the analogue peptides Regarding their biological activities, it was observed that the parental peptide TsAP-1 did not present antibacterial activity at the maximal concentration range tested. In contrast, the analogues butylatus-1 and -2 were capable of inhibiting susceptible Escherichia coli and Enterococcus faecalis at 5.3 and 43.1 µM respectively. Interestingly, the antibacterial potential of the butylatus-3 analogue was selective to E. coli KpC, at 39.6 µM. In terms of hemolytic properties, only butylatus-2 presented cellular hemolysis at 43.1 µM. Despite the reported data on the good performance of analogues peptides, butylatus-1 stands out as an excellent candidate in the development of a new alternative against infections caused by pathogenic bacteria, due to the high action potential of at low dosages and not shown hemolysis.NenhumaA alta incidência de infecções hospitalares, juntamente com o aumento exponencial de resistência bacteriana a múltiplas drogas, tem tornado necessária à busca de novas ferramentas para o controle desses patógenos. O presente trabalho apresenta o desenvolvimento e estudo dos peptídeos butylatus1, -2 e -3, que foram racionalmente projetados com base no peptídeo de escorpião Tityus serrulatus, TsAP-1, a fim de aumentar a atividade bactericida com diminuição da citotoxicidade. Os peptídeos análogos foram obtidos por meio de modificações pontuais de resíduos de aminoácidos baseados no padrão anfipático HHh+H (h+ : resíduos de aminoácidos hidrofílicos com carga positiva; H: resíduos de aminoácidos hidrofóbicos) encontrado no peptídeo parental de TsAP-1, reduzindo assim a hidrofobicidade e aumentando tanto o momento hidrofóbico como a carga líquida de cada sequência. Observou-se que o conteúdo helicoidal também aumentou, favorecendo o aumento da anfipacidade das moléculas. Em relação às suas atividades biológicas, observou-se que o peptídeo parental, TsAP-1, não apresentou atividade antibacteriana na maior concentração testada. Em contraste, os análogos butylatus-1 e -2 foram capazes de inibir linhagens de Escherichia coli suscetível e Enterococcus faecalis a 5,3 e 43,1 µM, respectivamente. Contudo, o potencial antibacteriano do análogo do butylatus-3 foi seletivo para E. coli KpC, a 39,6 µM. Em termos de propriedades hemolíticas, apenas o butylatus-2 apresentou hemólise celular a 43,1 µM. Apesar dos dados relatados sobre o bom desempenho dos peptídeos análogos, o butylatus-1 destacou-se como um excelente candidato no desenvolvimento de uma nova alternativa contra infecções causadas por bactérias patogênicas, devido ao seu alto potencial de ação bactericida em baixas doses e por não ser citotóxico para células eucarióticas.Universidade Federal da ParaíbaBrasilBiologia Celular e MolecularPrograma de Pós-Graduação em Biologia Celular e MolecularUFPBMigliolo, Ludovicohttp://lattes.cnpq.br/0805599101682606Luna, Karla Patricia de Oliveirahttp://lattes.cnpq.br/3043580578707915Flores, Taylla Michelle de Oliveira2021-05-10T20:17:06Z2019-11-182021-05-10T20:17:06Z2019-09-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttps://repositorio.ufpb.br/jspui/handle/123456789/20011porhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2021-06-21T14:37:06Zoai:repositorio.ufpb.br:123456789/20011Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2021-06-21T14:37:06Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
title |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
spellingShingle |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp Flores, Taylla Michelle de Oliveira Atividade microbiana Peptídeos antimicrobianos Toxina de escorpião Biofísica computacional Microbian activity Antimicrobial peptide Scorpion toxin Computational biophysics CNPQ::CIENCIAS BIOLOGICAS |
title_short |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
title_full |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
title_fullStr |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
title_full_unstemmed |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
title_sort |
Desenho racional de peptídeos antibacterianos análogos à toxina do escorpião Tityus sp |
author |
Flores, Taylla Michelle de Oliveira |
author_facet |
Flores, Taylla Michelle de Oliveira |
author_role |
author |
dc.contributor.none.fl_str_mv |
Migliolo, Ludovico http://lattes.cnpq.br/0805599101682606 Luna, Karla Patricia de Oliveira http://lattes.cnpq.br/3043580578707915 |
dc.contributor.author.fl_str_mv |
Flores, Taylla Michelle de Oliveira |
dc.subject.por.fl_str_mv |
Atividade microbiana Peptídeos antimicrobianos Toxina de escorpião Biofísica computacional Microbian activity Antimicrobial peptide Scorpion toxin Computational biophysics CNPQ::CIENCIAS BIOLOGICAS |
topic |
Atividade microbiana Peptídeos antimicrobianos Toxina de escorpião Biofísica computacional Microbian activity Antimicrobial peptide Scorpion toxin Computational biophysics CNPQ::CIENCIAS BIOLOGICAS |
description |
The high incidence of nosocomial infection, along with the advents of bacterial resistance to multiple drugs has increased exponentially, making it necessary the search for new tools to control these pathogens. The present study focuses on the development of butylatus-1, -2 and -3, which were rationally designed based on a scorpion’s peptide from Tityus serrulatus, named TsAP-1, in order to increase the bactericidal activity with a decrease in cytotoxicity. The analogue peptides were obtained through the punctual modification of amino acid residues based in an amphipathic pattern HHh+H (h+ : positively charged hydrophilic amino acid residues; H: hydrophobic amino acid residues) found in the TsAP-1 parental peptide, thereby reducing hydrophobicity and increasing both hydrophobic moment and net charge. It was observed that the helical content also increased, promoting the increase in amphipacity of the analogue peptides Regarding their biological activities, it was observed that the parental peptide TsAP-1 did not present antibacterial activity at the maximal concentration range tested. In contrast, the analogues butylatus-1 and -2 were capable of inhibiting susceptible Escherichia coli and Enterococcus faecalis at 5.3 and 43.1 µM respectively. Interestingly, the antibacterial potential of the butylatus-3 analogue was selective to E. coli KpC, at 39.6 µM. In terms of hemolytic properties, only butylatus-2 presented cellular hemolysis at 43.1 µM. Despite the reported data on the good performance of analogues peptides, butylatus-1 stands out as an excellent candidate in the development of a new alternative against infections caused by pathogenic bacteria, due to the high action potential of at low dosages and not shown hemolysis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-11-18 2019-09-27 2021-05-10T20:17:06Z 2021-05-10T20:17:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufpb.br/jspui/handle/123456789/20011 |
url |
https://repositorio.ufpb.br/jspui/handle/123456789/20011 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nd/3.0/br/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba Brasil Biologia Celular e Molecular Programa de Pós-Graduação em Biologia Celular e Molecular UFPB |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
institution |
UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
collection |
Biblioteca Digital de Teses e Dissertações da UFPB |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
repository.mail.fl_str_mv |
diretoria@ufpb.br|| diretoria@ufpb.br |
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1801842972740812800 |