Non-invasive 19F NMR analysis of a protein-templated N-acylhydrazone dynamic combinatorial library

Abstract

Dynamic combinatorial chemistry (DCC) is a powerful tool to identify ligands for biological targets. We used ¹⁹F NMR as an in situ, non-invasive technique for measuring the composition of a dynamic combinatorial library (DCL) of N-acylhydrazones (NAHs). An NAH DCL, constructed from a fluoro-aromatic aldehyde and a small set of hydrazides, was targetted at ecFabH, an essential enzyme in bacterial fatty acid biosynthesis. Our NMR analysis identified a tert-butyl NAH as the best binder which was confirmed by enzymatic assay.