At the molecular level, many diseases such as cancer and diabetes involve abnormal protein-protein interactions. Contrary to traditional thought, new research suggests that small molecules can antagonize specific protein-protein interactions. This represents a new paradigm in the pharmaceutical industry because protein-protein interactions are an unexplored context for lead compound discovery. Funding from National Institutes of Health will foster the research proposed here. This work serves multiple purposes. First, significant progress will be made towards the development of a drug that blocks the interaction of the tumorigenic cytokine Interleukin-2 (IL-2), with its receptor, IL-2Ralpha. Second, we will gain new insights into the nature of small molecule binding at protein interfaces. Third, we will develop a rapid and parallel method for discovering small-molecule/protein interactions across a broad range of targets.
| Thanos, Christopher D; DeLano, Warren L; Wells, James A (2006) Hot-spot mimicry of a cytokine receptor by a small molecule. Proc Natl Acad Sci U S A 103:15422-7 |
