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http://hdl.handle.net/1843/40939| Type: | Artigo de Periódico |
| Title: | Shortened derivatives from native antimicrobial peptide LyeTx I: in vitro and in vivo biological activity assessment |
| Authors: | Leonardo Lima Fuscaldi Joaquim Teixeira de Avelar Júnior Daniel Moreira dos Santos Daiane Boff Vívian Louise Soares de Oliveira Karla Aparecida Guimarães Gusmão Gomes Rosana de Carvalho Cruz Patrícia Luciana de Oliveira Paula Prazeres Magalhães Patricia Silva Cisalpino Luiz de Macêdo Farias Elaine Maria de Souza-Fagundes Johannes Delp Marcel Leist Jarbas Magalhães Resende Flávio Almeida Amaral Adriano Monteiro de Castro Pimenta Simone Odília Antunes Fernandes Valbert Nascimento Cardoso Maria Elena de Lima |
| Abstract: | In 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. |
| Subject: | Processo inflamatório Peptídeo antimicrobiano |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | FAR - DEPARTAMENTO DE ALIMENTOS FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA ICX - DEPARTAMENTO DE QUÍMICA |
| Rights: | Acesso Aberto |
| metadata.dc.identifier.doi: | 10.1177/1535370220966963 |
| URI: | http://hdl.handle.net/1843/40939 |
| Issue Date: | Feb-2021 |
| metadata.dc.url.externa: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885047/ |
| metadata.dc.relation.ispartof: | Experimental Biology and Medicine |
| Appears in Collections: | Artigo de Periódico |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Shortened derivatives from native antimicrobial peptide LyeTx I In vitro and in vivo biological activity assessment.pdf | 1.46 MB | Adobe PDF | View/Open |
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