Prospecting ligand for receptor activator proliferation of peroxisomes

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

Abstract

The pandemic of the metabolic syndrome affects at least 25% of the global population, characterized by a couple of associated pathological effects, such as diabetes, obesity, inflammation, an increase in cholesterol, and hypertension, which can result in cardiopathies, amongst other diseases. Currently, most of the efforts to combat this syndrome are 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, present unwanted effects. In this context, the scientific community and the pharmaceutical industries are in search of new substances that can bind to these receptors, modulating them selectively in an attempt to minimize the deleterious effects. The PPARs regulate the transcription of genes related to the metabolism of lipids, inflammation control, and insulin production. Their binders, faulty acids, eicosanoids, and dyslipidemias have been studied in the treatment of diabetes and dyslipidemias, 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 recombinant protein; (II) to Select substances according to their general structures of the binders, (such as rosiglitazone, for example); (III) to test these substances in the assay of transactivation in the culture of the mammalian cells; and (IV) attempt to crystalize the complexed receptor to more promising substances. It's important to highlight that these goals with immediate impact on 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 constitute one of the most used pharmacological classes for medical practice.(AU)