DNA-encoded libraries via late-stage functionalization strategies: a review

Abstract

The hit finding strategy in drug discovery has undergone a tremendous change in the past decade with the advent of DNA-encoded libraries with diverse chemical libraries. The miniaturization of the assays has enabled high-throughput screening on diverse targets to identify binders as a starting point for medicinal chemistry campaign. The diverse chemical space that can be accessed through DEL provides a unique opportunity to explore new chemistries on DNA. This review highlights the metal-mediated synthetic pathways that allow late-stage functionalisation of DNA strands to access such DEL libraries. Critical analysis of the literature and the methods employed has been done to allow readers to understand the usefulness, as well as the limitations of these protocols.