Avaliação estrutural e atividades antiproliferativa, antiviral, antiparasitária e antibacteriana dos peptídeos Stigmurina e TsAP-2 presentes na peçonha do escorpião Tityus stigmurus
The resistance to conventional drugs in diseases of infectious and neoplasic origin is a serious public health problem worldwide, presenting high morbidity and mortality, leading to an incessant search for new therapeutic agents in different natural sources. In this context, the scorpion venom co...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/32518 |
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| Resumo: | The resistance to conventional drugs in diseases of infectious and neoplasic origin is
a serious public health problem worldwide, presenting high morbidity and mortality,
leading to an incessant search for new therapeutic agents in different natural
sources. In this context, the scorpion venom constitutes a rich arsenal of bioactive
molecules, being non disulphide-bridged peptides (NDBPs) target of studies due to
its multifunctional actions. Stigmurin (FFSLIPSLVGGLISAFK-NH2, 1795.2 Da) and
TsAP-2 (FLGMIPGLIGGLISAFK-NH2, 1733.2 Da) are NDBPs identified on the
venom gland transcriptome of the Tityus stigmurus. Considering the multifunctional
action of NDBPS, in this study the three-dimensional structure of the Stigmurin was
elucidated by nuclear magnetic resonance and the antiproliferative,
immunomodulatory, antiparasitic, antiviral, antioxidant and antibiofilm activity of the
synthetic peptides Stigmurin and TsAP-2 were evaluated. The healing and antibiotic
effects of both peptides were evaluated by bacterial wound infection model in vivo, as
well as expanding the in vitro antibacterial potential of the TsAP-2. Stigmurin in
trifluoroethanol: water (40:60%) showed a random conformation in the N-terminal
region, with a helical structure from the seventh amino acid residue, being the first
NDBP present in the venom of scorpions of the genus Tityus with an elucidated
three-dimensional structure. Stigmurin and TsAP-2 revealed antiproliferative action
on neoplastic cells in non-toxic concentration for normal cells, modulating the release
of nitrite in murine macrophages stimulated by lipopolysaccharides. Stigmurin and
TsAP-2 did not demonstrate a leishmanicidal effect on the amastigote form of
Leishmania braziliensis. However, TsAP-2 revealed a high trypanocidal action of on
epimastigote and trypomastigote forms of Trypanosoma cruzi, and broad spectrum of
antibacterial action against Gram-positive and Gram-negative microorganisms. A
protective effect on primate renal epithelial cells against Zika virus infection was
demonstrated in the pretreatment assay for both peptides, revealing a high virucidal
action on herpes simplex virus type 1, with antiviral activity in post-infection assay. In
addition, Stigmurin and TsAP-2 were able to scavenge the hydroxyl radical in vitro at
concentration of 10 µM and 5 µM, respectivety, reducing its action in high
concentrations, suggesting the formation of agglomerates. Both peptides showed
antibiofilm activity, as well as antibacterial action in the skin wound infection model,
increasing the retraction rate of the lesion, suggesting the ability to induce tissue repair. In histopathological analysis, TsAP-2 promoted increased neovascularization
and re-epithelization, reducing necrosis in the surgical wound.The data suggest that
Stigmurin and TsAP-2 are promising multifunctional peptides for use as prototype to
obtaining new therapeutic agents. |
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