Schematic of a Dynamic Combinatorial Chemistry (DCC) experiment.
Identifying high-affinity small molecule binders for medically relevant drug targets typically involves the iterative synthesis of large numbers of compounds. What if we could set up a system whereby small molecule fragments could undergo recombination in the presence of the target of interest, thereby allowing selection and amplification of the highest affinity binder?
This idea, originally developed by a few labs (including ours) in the late 1990s, has developed into a vibrant field known as Dynamic Combinatorial Chemistry or Dynamic Covalent Chemistry (DCC). We are currently attempting to identify new chemical reactions that will allow us to expand the range of structures accessible to DCC, and to develop methods by which DCC can probe larger areas of chemical structure space.