Shortened derivatives from native antimicrobial peptide LyeTx I: in vitro and in vivo biological activity assessment

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dc.creatorLeonardo Lima Fuscaldi
dc.creatorJoaquim Teixeira de Avelar Júnior
dc.creatorDaniel Moreira dos Santos
dc.creatorDaiane Boff
dc.creatorVívian Louise Soares de Oliveira
dc.creatorKarla Aparecida Guimarães Gusmão Gomes
dc.creatorRosana de Carvalho Cruz
dc.creatorPatrícia Luciana de Oliveira
dc.creatorPaula Prazeres Magalhães
dc.creatorPatricia Silva Cisalpino
dc.creatorLuiz de Macêdo Farias
dc.creatorElaine Maria de Souza-Fagundes
dc.creatorJohannes Delp
dc.creatorMarcel Leist
dc.creatorJarbas Magalhães Resende
dc.creatorFlávio Almeida Amaral
dc.creatorAdriano Monteiro de Castro Pimenta
dc.creatorSimone Odília Antunes Fernandes
dc.creatorValbert Nascimento Cardoso
dc.creatorMaria Elena de Lima
dc.date.accessioned2022-04-08T21:43:12Z
dc.date.accessioned2025-09-08T23:55:37Z
dc.date.available2022-04-08T21:43:12Z
dc.date.issued2021-02
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doi10.1177/1535370220966963
dc.identifier.issn1535-3702
dc.identifier.urihttps://hdl.handle.net/1843/40939
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofExperimental Biology and Medicine
dc.rightsAcesso Aberto
dc.subjectProcesso inflamatório
dc.subjectPeptídeo antimicrobiano
dc.subject.otherInflammation process
dc.subject.otherInfection
dc.subject.otherSeptic arthritis
dc.subject.otherLyeTx I mnΔK
dc.subject.otherShortened derivatives from LyeTx I
dc.subject.otherAntimicrobial peptide
dc.titleShortened derivatives from native antimicrobial peptide LyeTx I: in vitro and in vivo biological activity assessment
dc.typeArtigo de periódico
local.citation.epage425
local.citation.issue1
local.citation.spage414
local.citation.volume246
local.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.
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ALIMENTOS
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
local.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885047/

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