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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/40939
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dc.creatorLeonardo Lima Fuscaldipt_BR
dc.creatorJoaquim Teixeira de Avelar Júniorpt_BR
dc.creatorDaniel Moreira dos Santospt_BR
dc.creatorDaiane Boffpt_BR
dc.creatorVívian Louise Soares de Oliveirapt_BR
dc.creatorKarla Aparecida Guimarães Gusmão Gomespt_BR
dc.creatorRosana de Carvalho Cruzpt_BR
dc.creatorPatrícia Luciana de Oliveirapt_BR
dc.creatorPaula Prazeres Magalhãespt_BR
dc.creatorPatricia Silva Cisalpinopt_BR
dc.creatorLuiz de Macêdo Fariaspt_BR
dc.creatorElaine Maria de Souza-Fagundespt_BR
dc.creatorJohannes Delppt_BR
dc.creatorMarcel Leistpt_BR
dc.creatorJarbas Magalhães Resendept_BR
dc.creatorFlávio Almeida Amaralpt_BR
dc.creatorAdriano Monteiro de Castro Pimentapt_BR
dc.creatorSimone Odília Antunes Fernandespt_BR
dc.creatorValbert Nascimento Cardosopt_BR
dc.creatorMaria Elena de Limapt_BR
dc.date.accessioned2022-04-08T21:43:12Z-
dc.date.available2022-04-08T21:43:12Z-
dc.date.issued2021-02-
dc.citation.volume246pt_BR
dc.citation.issue1pt_BR
dc.citation.spage414pt_BR
dc.citation.epage425pt_BR
dc.identifier.doi10.1177/1535370220966963pt_BR
dc.identifier.issn1535-3702pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/40939-
dc.description.resumoIn the continuing search for novel antibiotics, antimicrobial peptides are promising molecules, due to different mechanisms of action compared to classic antibiotics and to their selectivity for interaction with microorganism cells rather than with mammalian cells. Previously, our research group has isolated the antimicrobial peptide LyeTx I from the venom of the spider Lycosa erythrognatha. Here, we proposed to synthesize three novel shortened derivatives from LyeTx I (LyeTx I mn; LyeTx I mnΔK; LyeTx I mnΔKAc) and to evaluate their toxicity and biological activity as potential antimicrobial agents. Peptides were synthetized by Fmoc strategy and circular dichroism analysis was performed, showing that the three novel shortened derivatives may present membranolytic activity, like the original LyeTx I, once they folded as an alpha helix in 2.2.2-trifluorethanol and sodium dodecyl sulfate. In vitro assays revealed that the shortened derivative LyeTx I mnΔK presents the best score between antimicrobial (↓ MIC) and hemolytic (↑ EC50) activities among the synthetized shortened derivatives, and LUHMES cell-based NeuriTox test showed that it is less neurotoxic than the original LyeTx I (EC50 [LyeTx I mnΔK] ⋙ EC50 [LyeTx I]). In vivo data, obtained in a mouse model of septic arthritis induced by Staphylococcus aureus, showed that LyeTx I mnΔK is able to reduce infection, as demonstrated by bacterial recovery assay (∼10-fold reduction) and scintigraphic imaging (less technetium-99m labeled-Ceftizoxime uptake by infectious site). Infection reduction led to inflammatory process and pain decreases, as shown by immune cells recruitment reduction and threshold nociception increment, when compared to positive control group. Therefore, among the three shortened peptide derivatives, LyeTx I mnΔK is the best candidate as antimicrobial agent, due to its smaller amino acid sequence and toxicity, and its greater biological activity.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Geraispt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentFAR - DEPARTAMENTO DE ALIMENTOSpt_BR
dc.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASpt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIApt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICApt_BR
dc.publisher.departmentICX - DEPARTAMENTO DE QUÍMICApt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofExperimental Biology and Medicinept_BR
dc.rightsAcesso Abertopt_BR
dc.subjectInflammation processpt_BR
dc.subjectInfectionpt_BR
dc.subjectSeptic arthritispt_BR
dc.subjectLyeTx I mnΔKpt_BR
dc.subjectShortened derivatives from LyeTx Ipt_BR
dc.subjectAntimicrobial peptidept_BR
dc.subject.otherProcesso inflamatóriopt_BR
dc.subject.otherPeptídeo antimicrobianopt_BR
dc.titleShortened derivatives from native antimicrobial peptide LyeTx I: in vitro and in vivo biological activity assessmentpt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885047/pt_BR
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