Engineering orthogonal ligand-receptor pairs from "near drugs".

  title={Engineering orthogonal ligand-receptor pairs from "near drugs".},
  author={Donald Francis Doyle and Dwaine A Braasch and Laurie K. Jackson and Holly E. Weiss and Marcus F. Boehm and David J Mangelsdorf and David R. Corey},
  journal={Journal of the American Chemical Society},
  volume={123 46},
Cell-permeable small molecules are powerful tools for unraveling complex cellular pathways. We demonstrate that nuclear hormone receptors can be engineered through mutagenesis to create orthogonal ligand-receptor pairs to control transcription. Mutated residues in the retinoid X receptor (RXR) were chosen from structural analysis of RXR and the retinoic acid receptor (RAR) ligand binding domains. The potential ligands screened for activation of variant receptors are "near drugs"--compounds… CONTINUE READING