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- ItemSomente MetadadadosEstudo da atividade antimicrobiana da crotamina nativa e sintetica, do seu analogo recombinante e fragmentos peptidicos(Universidade Federal de São Paulo (UNIFESP), 2010) Yamane, Erica Sayuri [UNIFESP]A crotamina e uma miotoxina presente no veneno da cascavel sulamericana Crotalus durissus terrificus capaz de promover a imobilizacao das patas traseiras de roedores. Esta toxina possui baixo peso molecular e alto conteudo de aminoacidos basicos como a lisina e a arginina, alem de seis residuos de cisteina formando tres pontes dissulfeto. A crotamina apresenta o mesmo padrao de distribuicao de pontes de dissulfeto observado nas β- defensinas, que sao peptideos antimicrobianos encontrados na epiderme de mamiferos e que apresentam conhecida atividade antimicrobiana. Este fato, e apesar da diferenca na estrutura/sequencia primaria da crotamina e da β- defensina, nos levou a estudar a possivel atividade antimicrobiana da crotamina. Considerando que a crotamina e obtida unicamente a partir da sua purificacao do veneno da cascavel sendo, portanto, totalmente dependente da extracao do veneno de serpentes mantidas em cativeiro ou capturadas na natureza, este trabalho teve como objetivo estudar fontes alternativas de obtencao de crotamina e caracterizar suas atividades funcionais, incluindo a atividade antimicrobiana e ensaio in vivo de imobilizacao das patas traseiras. Os ensaios de atividade antimicrobiana foram realizados com a crotamina natural, recombinante, sintetica, e seus fragmentos peptidicos (P1 e P2) contra bacterias Gram-postiva e Gram-negativa e, fungos. Foi observado uma atividade mais pronunciada contra varias especies de fungo, especialmente do genero Candida.No ensaio de imobilizacao das patas traseiras foram testadas a crotamina natural, a sintetica e o fragmento peptidico P1, na dose de 2,5 mg/kg em camundongos Swiss adultos. Nesta dose foi possivel observar a paralisia das patas destes animais somente apos a injecao da crotamina natural, como ja descrito na literatura e, da crotamina sintetica. O fragmento peptidico nao causou nenhuma modificacao no comportamento dos animais
- ItemSomente MetadadadosEstudo dos requisitos estruturais para a atividade biologica da gomesina(Universidade Federal de São Paulo (UNIFESP), 2005) Fazio, Marcos Antonio [UNIFESP]
- ItemAcesso aberto (Open Access)Relação de alterações conformacionais da prolil oligopeptidase devido a interação com a α – sinucleína(Universidade Federal de São Paulo (UNIFESP), 2019-09-26) Santos, Gabriel Silva [UNIFESP]; Oliveira, Vitor Marcelo Silveira Bueno Brandao De [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Prolyl oligopeptidase (EC 3.4.21.26, POP) is a serine peptidase, involved in the metabolism of neuropeptides and peptide hormones. In vitro and in vivo studies show that POP interacts with alpha synuclein (syn) by accelerating the aggregation of this protein, although when prolyl oligopeptidase is inhibited, syn aggregation is reduced. This mechanism for POP's participation in syn aggregation is totally unknown. The structure of POP does not allow peptides larger than 30 amino acid residues or proteins to reach their active center. Data from the literature show that POP presents an open (catalytic and regulatory domain shift with active center exposure) and a closed (catalytic and regulatory domain approach) conformation. The overall objective of this project was to study this possible "open and close" movement that may occur in POP due to interaction with substrates or inhibitors, and the implication of this conformational change in interaction with alpha synuclein. For this purpose, spectroscopic probes were used, when nearby they have characteristic fluorescence emission, excimer, in order to evaluate the conformational movements of POP and the possible implication of these movements in the interaction with syn. To validate the applied methodology, we used Thimet Oligopeptidase (TOP) a protein widely studied in our research group. The use of TOP provided important data for the use of spectroscopic probes showing that the separation of oligomeric species is fundamental for the analyzes studied here. The proteins with the spectroscopic probes showed activity, indicating that the tertiary structure was not impaired and consequently its function. Probe approximation with increasing guanidine chloride concentration showing probe spacing and excimer disappearance were evaluated. In addition, we evaluated by circular dichroism the POP - syn interaction and the hydrolysis profile of POP in the presence of syn. Interestingly, the high concentration of syn hinders substrate access to the active center, and the interaction between proteins occurs a change in secondary structure
- ItemAcesso aberto (Open Access)Relação Estrutura-Atividade de Fragmentos da Leptina(Universidade Federal de São Paulo (UNIFESP), 2008-03-26) Martins, Marta Natividade Crizol [UNIFESP]; Miranda, Antonio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The protein hormone produced by the ob-gene and denominated leptin, a product originating from adipose tissue, circulates in the plasma and affects the energy balance by interacting with the hypothalamus. Leptin plays an important role in the regulation of a variety of physiological functions, including food intake, body temperature and body weight maintenance. Total absence or resistance to leptin causes morbid obesity, diabetes and hypogonadism. The tertiary structure of the leptin molecule reveals the existence of a fourhelix bundle that is characteristic of the short-helix cytokines. To identify regions of the leptin molecule responsible for its bioactivity, we have synthesized six peptides based on the protein three-dimensional structure. Our results indicated that the fragments AchLEP92- 115-NH2 (IV) and Ac-[Ser117]-hLEP116-140-NH2 (V) were recognized by leptin receptor present in hp-75 cells, in agreement with the obtained by other authors, validating that this region of the molecule contain the functional epitope of the leptin molecule. In the present study, a new series of peptides encompassing the region of fragments IV and V of leptin were synthesized, and their effects on body weight and food intake were assessed when administered into the lateral cerebroventricle of normal rats. Peptides were synthesized by the solid phase methodology, purified by RP-HPLC and characterized by LC/ESI-MS. We also performed a conformational study of the peptides by circular dichroism in order to correlate the biological activity and secondary structure of the leptin fragments. Out off the new series of compounds, the best results were obtained with the fragment Ac-hLEP110-119-NH2 (VI) which showed to be more active than leptin and equipotent to [D-Leu4]-OB3 the most active leptin fragment described in the literature so far. Although the peptide fragments design needs refinement, this kind of approach may offer the basis for the development of leptin-related compounds with potential application in human obesity or veterinary medicine.
- ItemSomente MetadadadosSíntese e relação estrutura-atividade de análogos da angiotensina II, bradicinina e hormônio estimulador de melanócito contendo marcador spin através dos métodos da ressonância paramagnética e do dicroísmo circular(Universidade Federal de São Paulo (UNIFESP), 2000) Barbosa, Simone dos Reis [UNIFESP]; Nakaie, Clovis Ryuichi [UNIFESP]
- ItemSomente MetadadadosSintese, estudos biologicos e conformacionais de analogos da angiotensina II e bradicinina contendo um marcador de spin com estrutura do tipo pirrolidina(Universidade Federal de São Paulo (UNIFESP), 2005) Poletti, Erick Fernando [UNIFESP]
- ItemSomente MetadadadosSintese, estudos biologicos e conformacionais, em solucao e em sistemas membrana-mimeticos, de peptideos contendo aminoacido paramagnetico(Universidade Federal de São Paulo (UNIFESP), 2004) Vieira, Renata de Freitas Fischer [UNIFESP]