Innovative Drug Discovery and Nanotechnology (Track)

GFP chromophores as potential ligands for the Estrogen Receptor and the Pregnane X Receptor

Bahareh Azizi
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA


Abstract:

Nuclear receptors are ligand activated transcription factors involved in various biological processes, such as differentiation and development, and are implicated in several diseases, such as cancer and diabetes. In fact, 10-15% of the commonly prescribed drugs in the current market are nuclear receptor ligands, such as Tamoxifen, currently a major component of breast cancer therapy. Thus, a need for novel small molecule ligands that can serve as potential nuclear receptor drugs are of vast interest. To develop a novel class of nuclear receptor ligands, derivatives of GFP chromophores were synthesized based upon an arylideneimidazolone for the Estrogen Receptor and the Pregnane X Receptor. These compounds display binding and activation in both yeast and human embryonic kidney cells (HEK293T cells). As derivatives of the GFP chromophore, these ligands also have the ability to fluoresce, providing the added benefit of visualization of nuclear receptor expression in cells. A few of the designed GFP chromophores display fluorescence upon binding. Thus, further development of GFP chromophores as potential ligands for various members of the nuclear receptor superfamily not only provide a new class of potential drugs, but provide a tool for visualizing nuclear receptor mobility and trafficking in vivo.