BIOL 151 |
| Altered transcriptional patterns are associated with all human diseases, either as a 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. Despite the complexity of the transcriptional regulatory system, the design principles for the identification of small molecules that activate this process are evidently straightforward. We find that several structurally distinct amphipathic molecular scaffolds can function in vitro and in human cells as transcriptional activation domains. 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 tuning the potency of the small molecules as well as their gene- and tissue-targeting properties will be discussed. |
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Eli Lilly Award Symposium
9:00 AM-11:40 AM, Wednesday, August 22, 2007 BCEC -- 109A, Oral
Division of Biological Chemistry |