Estudos estruturais e biológicos do peptídeo StigA15 e a relação com o protótipo natural Stigmurina
Due to the broad spectrum of biological activities reported in the literature for peptides present in scorpion venoms, an increase in the studies of these molecules has been observed, especially of antimicrobial peptides, which are investigated as strategic alternatives to face problems such as r...
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| Formato: | Dissertação |
| Idioma: | pt_BR |
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Brasil
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/28126 |
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| Resumo: | Due to the broad spectrum of biological activities reported in the literature for peptides
present in scorpion venoms, an increase in the studies of these molecules has been
observed, especially of antimicrobial peptides, which are investigated as strategic
alternatives to face problems such as resistance to conventional antibiotics. It is known
that the mechanism of action of antimicrobial peptides occurs in large part by the
interaction with microorganism membrane, causing destabilization of the lipid bilayer and
resulting in the formation of pores, which lead to cell lysis. However, details of these
interactions are not yet completely known and significant variation may occur from
peptide to peptide, therefore, membrane-peptide interaction studies with biomimetic
environments are necessary. The present study proposes the synthesis and chemical
characterization of the bioactive peptide StigA15, designed from the primary sequence
of Stigmurin, antimicrobial peptide identified from Tityus stigmurus transcriptome. The
peptide was obtained from Fmoc solid phase peptide synthesis. Isothermal Titration
Calorimetry (ITC), Circular Dichroism (CD) and Nuclear Magnetic Resonance (NMR)
spectroscopy were used as the main research tools and the respective experiments were
performed in mimetic membrane environments. The activity of StigA15 when compared
to Stigmurin revealed that the substitution of two serine residues by two charged lysines
resulted in higher activities against Gram-positive and Gram-negative bacteria, as well
as against fungi. According to preliminary studies, it has been identified that StigA15 has
a higher hydrophobic moment and therefore could be inserted more deeply in the
membrane than Stigmurin. StigA15 presents selectivity towards pattogen cells, since it
presents very low hemolysis rates at the active antimicrobial concentrations. This
selectivity is further supported by ITC experiments that indicated significatly stronger
interactions of StigA15 with anionic vesicles, when compared to zwitterionic vesicles. CD
and NMR spectroscopies indicated that the peptide adopts helical conformations in
membrane mimetic enviorenments. In addition, NMR spectroscopy proved that the
peptide shows high amphipathicity which is, together with its net positive charge (+4), a
feature commonly found in several antimicrobial peptide sequences. Therefore, here is
presented a novel peptide sequence with high biotechnological potential. |
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