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Previous issue date: 2017-11-28 / Tityus stigmurus corresponde ? esp?cie de escorpi?o predominante na regi?o Nordeste do Brasil, sendo considerado um dos principais causadores de acidentes escorpi?nicos. Na pe?onha do T. stigmurus, que ? composta de uma mistura complexa de mol?culas de alta e baixa massa molecular, foi identificado e caracterizado um pept?deo antimicrobiano denominado Stigmurina (FFSLIPSLVGGLISAFK-NH2). Pept?deos antimicrobianos s?o pequenas mol?culas consideradas a primeira linha de defesa contra micro-organismos, apresentando amplo espectro de a??o antimicrobiana. A literatura reporta tamb?m a atividade desses pept?deos contra c?lulas cancer?genas. Sequ?ncias nativas de pept?deos bioativos como prot?tipo para a obten??o de novas mol?culas t?m sido utilizadas com o intuito de potencializar a sua atividade e reduzir a toxicidade. Nesse contexto, realizou-se a caracteriza??o estrutural in silico e por dicro?smo circular, bem como a avalia??o da atividade antimicrobiana, antiparasit?ria, antiproliferativa e hemol?tica de dois pept?deos an?logos obtidos ? partir da Stigmurina, denominados StigA3 e StigA4. A an?lise da conforma??o tridimensional in silico do StigA3 e StigA4 demonstrou uma estrutura helicoidal, sendo este resultado confirmado por dicro?smo circular. O aumento da carga superficial e do momento hidrof?bico de ambos os pept?deos an?logos quando comparado com a Stigmurina resultaram na potencializa??o da atividade antimicrobiana e antiparasit?ria. Os pept?deos StigA3 e StigA4 apresentaram a??o antiproliferativa semelhante ao pept?deo nativo, com exce??o para a c?lula normal, para qual os pept?deos an?logos se mostraram menos t?xicos. Portanto, estes resultados indicam uma potencial aplica??o terap?utica destes pept?deos an?logos, demonstrando a efici?ncia do desenho racional de f?rmacos para a obten??o de novos agentes antiproliferativos e anti-infecciosos. / Tityus stigmurus it?s the predominant scorpion specie in Northeast region from Brazil, it?s considered one of the main cause of scorpion accidents in this region. In T. stigmurus venom, which is a complex mixture of high and low molecular mass molecules, was identified an antimicrobial peptide denominated Stigmurin. Antimicrobial peptides are small molecules considered the first line of defense against microorganisms, they show broad spectrum action. Many authors have proved that these peptides can also be effective on cancerous cells. Mutation in these molecules sequence has been held aiming the increase in the activity maintaining its low toxicity. Therefore, it is proposed the characterization of the structure in silico and by circular dichroism, as well the antimicrobial, antiparasitic, anti-proliferative and hemolytic activities of two analog peptides from Stigmurin, denominated StigA3 and StigA4. We performed an in silico analysis for these peptides, where we were able to observe ?-helix structure, which was confirmed by circular dichroism. We were also able to find that the analog peptides net charge and hydrophobic moment were higher than Sitgmurin?s, which can explain the increase in antimicrobial and antiparasitic activity. The peptides StigA3 e StigA4 showed activity on cancerous cells similiar to the native peptide, except when tested on a normal cell we were able to find that they?re less toxic. Therefore, these results indicate a potential biotechnological application for the analogs peptides, even as prototype to new therapeutic agents.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/24992 |
| Date | 28 November 2017 |
| Creators | Parente, Adriana Marina e Silva |
| Contributors | 96728647449, Salvador, Daniela Priscila Marchi, 26757993864, Silva, Marcelo de Sousa da, 85074276420, Pedrosa, Matheus de Freitas Fernandes |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM BIOQU?MICA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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