Drug discovery by dynamic combinatorial libraries.

Abstract

Dynamic combinatorial chemistry is a recently introduced supramolecular approach that uses self-assembly processes to generate libraries of chemical compounds. In contrast to the stepwise methodology of classical combinatorial techniques, dynamic combinatorial chemistry allows for the generation of libraries based on the continuous interconversion between the library constituents. Spontaneous assembly of the building blocks through reversible chemical reactions virtually encompasses all possible combinations, and allows the establishment of adaptive processes owing to the dynamic interchange of the library constituents. Addition of the target ligand or receptor creates a driving force that favours the formation of the best-binding constituent--a self-screening process that is capable, in principle, of accelerating the identification of lead compounds for drug discovery.