We study architectural aspects of building molecules. This is expressed through exercises in total synthesis, the development of reactions and processes, and in attempts to generally emulate small-molecule biosynthetic schemes. We seek to create new structures in new ways, and for those molecules to have valuable biological functions.
Evolution provides chemists much inspiration and opportunity. We explore the synthesis of small molecule natural products, in particular those having special structures and potentially valuable pharmacology. Current interests include unusual antimicrobial trithiocanes isolated from a marine tunicate, complex prodigiosins that can bind microRNA, spirocyclic imines that initiate apoptosis selectively and various other exotic bioactive substances.
The chemistry and biology of natural products is prominent in the group. We’re also involved in new tactics to create non-natural molecules – particularly those able to fuel discovery in areas of biochemistry where drug-like heterocycles and/or toxins can be limited. Specific and potent agonists/antagonists of intracellular protein-protein interactions are of particular interest.
We interface our chemistry with biological research in numerous ways. We screen complex molecule collections in silico and experimentally, searching for new functions in cytokine signaling, stem cell differentiation, cell death regulation, and hormone mimicry. We also study the biology of specific compounds.