Event Information
Small Molecule Control of Gene Activation
- Abstract:
Artificial transcriptional regulators are powerful tools for developing a more detailed picture of the protein-protein and protein-DNA interactions that govern gene expression. Given the wide range of human diseases linked to aberrant transcription patterns, artificial regulators also hold great promise for the long-term development of transcription-targeted therapeutic agents. The greatest challenges in this arena are twofold: 1. the identification of small molecules that can reconstitute the function of transcriptional activators; and 2. the development of artificial transcriptional activators that function robustly in a cellular environment. Towards that end, mechanistic studies in vitro and in S. cerevisiae were used to delineate the relative importance of transcriptional activator characteristics that dictate functional potency, including target binding site(s), target affinity, and transcriptional activator lifetime. This data was used to design small molecules that function as transcriptional activation domains in vitro and in cell culture. Structural studies of these molecules in complex with transcriptional machinery proteins reveal that they target the binding surfaces used by natural transcriptional activators. The general principles for increasing the potency of the small molecules as well as their gene targeting properties will be discussed.
Host: David Beratan
Chemistry Seminar