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Prospecting ligand for receptor activator proliferation of peroxisomes

Grant number: 12/10510-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2012
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Ana Carolina Migliorini Figueira
Grantee:Aline Villanova Bridi
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil

Abstract

The pandemic of the metabolic syndrom affects at least 25% of the global population, characterized by a couple of associated pathological effects, such as diabetes, obesity, inflammation, an increase of cholesterol and hypertension, which can result in cardiopathies, amongst other diseases. Currently, most of the efforts to combat this syndrome is reflected in attempts to control nuclear receptors especially TR and PPAR. However, the majority of the drug available on the market, which uses these receptors as targets, presents unwanted effects. In this context, the scientific community and the pharmaceutical industries are in search of new substances that can bind of these receptors, modulating them selectively in the attempt to minimize the deleterious effects. The PPARs regulate the transcription of genes related to the metabolism of lipids, inflammation control control and insulin production. Their binders, falty acids, eicosanoids and dislipidemias have been studied in the treatment of diabetes and dislipidemias, being of great importance to the pharmaceutical industry. In this context, the objective of this project is to find some substances that can act as PPAR agonists. For such, it's necessary (i) to express and purify the recombinat protein; (ii) Select substances according to their general structures of the binders, (such as rosiglitazone, for example); (iii) test these substances in assay of transactivation in culture of the mammalian cells; and (iv) attempt to cristalize the complexed receptor to more promising substances . It's important to highlight that these goals with immediate impact in the search for rational PPAR agonist or antagonists, and is included in a perspective of the promotion of the scientific technological development in the area of nuclear receptors; with narrow relations to the interests of the pharmaceutical industry, medicine and the production sector. We intend to reach some leader substances for the rational planning of drugs in the combat against metabolic syndromes, which currently constitud one of the most used pharmacological classes for medical practice.