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

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2021

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Fuscaldi, Leonardo Lima
Teixeira de Avelar Júnior, Joaquim
Moreira Dos Santos, Daniel
Boff, Daiane
Soares de Oliveira, Vívian Louise
Guimarães Gusmão Gomes, Karla Aparecida
de Carvalho Cruz, Rosana
de Oliveira, Patrícia Luciana
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Experimental Biology and Medicine. Sage Publications. 2021, 246(4), pp. 414-425. ISSN 1535-3702. eISSN 1535-3699. Available under: doi: 10.1177/1535370220966963

Zusammenfassung

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.

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570 Biowissenschaften, Biologie

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Antimicrobial peptide, shortened derivatives from LyeTx I, LyeTx I mnΔK, septic arthritis, infection, inflammation process

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ISO 690FUSCALDI, Leonardo Lima, 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, Johannes DELP, Marcel LEIST, 2021. Shortened derivatives from native antimicrobial peptide LyeTx I : In vitro and in vivo biological activity assessment. In: Experimental Biology and Medicine. Sage Publications. 2021, 246(4), pp. 414-425. ISSN 1535-3702. eISSN 1535-3699. Available under: doi: 10.1177/1535370220966963
BibTex
@article{Fuscaldi2021Short-51821,
  year={2021},
  doi={10.1177/1535370220966963},
  title={Shortened derivatives from native antimicrobial peptide LyeTx I : In vitro and in vivo biological activity assessment},
  number={4},
  volume={246},
  issn={1535-3702},
  journal={Experimental Biology and Medicine},
  pages={414--425},
  author={Fuscaldi, Leonardo Lima and Teixeira de Avelar Júnior, Joaquim and Moreira Dos Santos, Daniel and Boff, Daiane and Soares de Oliveira, Vívian Louise and Guimarães Gusmão Gomes, Karla Aparecida and de Carvalho Cruz, Rosana and de Oliveira, Patrícia Luciana and Delp, Johannes and Leist, Marcel}
}
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