Small molecule-protein interactions play important roles in modulating wide ranges of biological processes, such as cell growth/death, differentiation and development. Which cellular pathways do they affect? How do they work at the molecular level? What is the structural basis for their specific activity? How can we control them? Answers to these questions should lead to advances in our fundamental understanding of the biological properties of small molecules as well as in the drug development. In addition, they may contribute to the discovery of novel biological processes.

Our research group is interested in developing new chemical probes by organic synthesis to investigate the mechanism of action of small molecules and natural products with anticancer activity. A particular focus is on the design and synthesis of novel gold-nanoparticle probes to covalently capture and isolate target proteins from the complex cellular context. Identification of target proteins represents the critical first step in understanding how a bioactive small molecule exerts its function. However, it has so far has been rather a slow and laborious trial and error process and is one of the outstanding problems in chemical biology. We aim to provide a general method to accelerate the discovery of cellular targets of small-molecules and natural products.