ReviewPost-screenDNA-encoded chemical libraries: foundations and applications in lead discovery

•DNA-encoded chemical libraries: powerful means for hit identification in pharma.•Link between the chemical building block and an amplifiable genetic barcode.•Production of millions of compounds within a few weeks.•Screening of libraries in a single test tube against proteins of pharmaceutical interest.•Numerous protein binders have thus far been identified by this technique.

DNA-encoded chemical libraries have emerged as a powerful tool for hit identification in the pharmaceutical industry and in academia. Similar to biological display techniques (such as phage display technology), DNA-encoded chemical libraries contain a link between the displayed chemical building block and an amplifiable genetic barcode on DNA. Using routine procedures, libraries containing millions to billions of compounds can be easily produced within a few weeks. The resulting compound libraries are screened in a single test tube against proteins of pharmaceutical interest and hits can be identified by PCR amplification of DNA barcodes and subsequent high-throughput sequencing.