Desenvolvimento de metodologia para a avaliação da qualidade da stigmurina, um peptídeo do escorpião Tityus stigmurus
Stigmurin is a peptide containing 17 amino acids (FFSLIPSLVGGLISAFK-NH2) identified in the transcriptome of the scorpion Tityus stigmurus, synthetized with amidated C-terminal end. It has shown antimicrobial action against Gram-positive and Gram negative bacterial, some methicillin resistant bact...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Brasil
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/28375 |
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| Resumo: | Stigmurin is a peptide containing 17 amino acids (FFSLIPSLVGGLISAFK-NH2)
identified in the transcriptome of the scorpion Tityus stigmurus, synthetized with
amidated C-terminal end. It has shown antimicrobial action against Gram-positive and
Gram negative bacterial, some methicillin resistant bacterial, efficient in controlling
sepsis, antiparasitic action for epimastigote forms T. cruzi Y strain and low
antihemolytic activity. This doctoral thesis deals the development of analytical
methodologies for the quality assessment of the synthetic peptide stigmurin, identified
in the Tityus stigmurus scorpion venom. The techniques used were analytical
techniques (DSC, TG, TG-FTIR), chromatography (HPLC, LC-MS, GC-MS pyrolysis)
and complementary techniques (SEM, FTIR and XRD). Synthetic solid-state Stigmurin
present amorphous form, with a glass transition temperature of 149 °C (midpoint) and
the initial temperature differing between nitrogen atmosphere (183 °C) and synthetic
air (180 °C). Thermal decomposition produces mainly volatiles derived from
phenylalanine, proline, serine and leucine residues, which seems to start in its Nterminus. Synthesis impurities were detected due to coupling errors, serine and
isoleucine / leucine deletion, and lack of amidation at the N-terminal end. During
thermal decomposition were detected y fragments, such as: y14 (m/z = 1.413,8776 Da),
y15 (m/z = 1.500,9121 Da), fragments resulting from neutral losses of ammonium and
water (m/z = 1.778,0184 Da e 1.760,0041 Da) and series b fragments, possibly derived
from fragments b6 and b2 (m/z = 566,4267, m/z = 679,5107, m/z = 274,2737 and m/z
= 290.2686 Da). Samples obtained after heating stigmurine to temperatures of 190 °C
and 230 °C, with residual stigmurine content of 60% and 0%, respectively, showed
antiparasitic activity possibly related to the decomposition products formed and / or the
trapping of toxic gases during thermal decomposition. This thesis provides support for
the elaboration of technological strategies aimed at maintaining quality, safety and
efficacy during the development of future pharmaceutical products. |
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