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Synthesis and structural and functional studies of new ligands for nuclear receptors of thyroid hormones

Grant number: 06/06657-8
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): April 01, 2007
Effective date (End): March 31, 2010
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Igor Polikarpov
Grantee:Mirela Inês de Sairre
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Thyroid hormones (TH) are involved in the normal differentiation, growth, and metabolism of several tissues in all vertebrates. Their actions are mediated by the thyroid hormone receptors (TRs), members of the nuclear hormone receptor superfamily. These receptors are transcription factors that bind to DNA through specific sequences, the so-called TR response element (TREs), in promoters of target genes. The pharmacological effects of TH allow their use in the treatment of some disorders; however, there generally are undesirable adverse effects. Therefore, in this work, we propose the synthesis of new ligands (agonist/antagonist) that should be potentially useful for treatment of various disorders. Moreover, structural and functional studies by means of crystallographic analysis of the TRs associated with the new ligands obtained in this project will also be carried out. (AU)