DNA-encoded library

Imagine every product in a giant warehouse carried a unique barcode, so you could mix everything into one bin, ask 'who sticks to this target?', and then read the barcodes of the winners to learn exactly what they were. A DNA-encoded library does this for chemistry: each compound is physically attached to a short, unique strand of DNA that records its synthetic history like a barcode.

Because the DNA tag identifies the molecule, the whole library — often millions to billions of distinct compounds — can be pooled and screened together in a single tube. The target (usually a purified protein) is exposed to the mixture; molecules that bind are captured, the non-binders are washed away, and the DNA tags of the survivors are amplified and read by sequencing. The barcodes that appear most often point to the compounds that bound best.

DELs give access to staggering numbers of compounds at low cost, but the trade-offs are real: the DNA tag itself can influence binding, hits must be re-made without the DNA to confirm they truly work ('off-DNA' resynthesis), and the readout is enrichment, not a clean activity number. Like all screening, a DEL produces leads to be validated, not finished answers.