Chemical control of gene activation

ORGN 538

Anna K. Mapp, amapp@umich.edu, Department of Chemistry, University of Michigan, 930 N University, Ann Arbor, MI 48109-1055
Altered transcriptional patterns are associated with all human diseases, either as the cause of the disease or as an effect. For this reason, molecules that interfere with or promote protein-protein interactions within the transcriptional regulatory network are attractive targets for therapeutic development and as mechanistic probes. Here we show that several low molecular weight amphipathic scaffolds reconstitute the function of natural activators in vitro and in human cell culture. In addition, 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.