Protein directed dynamic combinatorial chemistry: an efficient strategy for drug discovery

1 p.The conventional methodology for drug discovery is to find a chemical compound for a specific target. However, an alternative approach based on the design of systems where targets direct the synthesis of their best binders has emerged as Protein-directed Dynamic Combinatorial Chemistry (PD-DCC). In PD-DCC, selected building blocks react with each other through reversible chemical reactions providing mixtures of oligomers (Dynamic combinatorial libraries,DCLs). Due to its ability to respond to external stimuli, proteins can change the equlibrium towards the formation of their high-affinity compounds, changing the distribution of each specie.This approach selects directly ligands, therefore, the drug discovery process is accelerated. Here we report the identification of a non-competitive inhibitor of Glucose oxidase, using a dynamic combinatorial approach through thiol-disulfide exchange at low temperature and physiological conditions.Peer reviewe