DNA-Encoded Fragment Libraries: Dynamic Assembly, Single-Molecule Detection, and High-Throughput Hit Validation

An urgent challenge in chemistry and biotechnology is to develop a routine, robust, and cost-effective method for the identification of molecules that specifically bind to a large variety of protein targets. In recent years, an elegant selection method for small-molecule drug discovery, DNA-encoded chemical library (DECL) technology, has been receiving much attention from the pharmaceutical and biotechnology industries. Here, we review the major recent developments in DECL technology, with a focus on the self-assembling dual-display format, which aims to combine the bio-inspired selection process with a fragment-based approach to discover potent binders to protein targets.