Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry

Protein-templated dynamic combinatorial chemistry (DCC) has emerged as a powerful method to identify new inhibitors given that it enables the protein to select its own best binder(s) from a library of interconverting compounds. Since the first report of DCC applied to the discovery of binders for a protein, this elegant tool has been employed on a range of protein targets in early stage of medicinal-chemistry projects. A toolbox with various reversible and biocompatible reactions has become available, and the portfolio of analytical techniques is growing. Despite progress, in most cases, the libraries employed remain of moderate size due to difficulties associated with their analysis. In this article, analytical methods used in protein-templated DCC are described using examples of recent developments and reports.