A novel protocol to accelerate dynamic combinatorial chemistry via isolation of ligand-target adducts from dynamic combinatorial libraries: A case study identifying competitive inhibitors of lysozyme

A novel protocol based on size-exclusion chromatography (SEC) and MS was established to accelerate dynamic combinatorial chemistry (DCC) in this study. By isolating ligand-target adducts from the dynamic combinatorial library (DCL), ligands could be identified directly by MS after denaturation. Three new inhibitors for lysozyme were discovered by this SEC-MS protocol in a case study. Km Data for these new inhibitors was also determined.