Fig. 1. (a) Previous work: two sets of DNA-linked fragments form dynamically exchanging duplexes; addition of the target enriches high affinity duplexes.49,67,68 (b) DNA-encoded dynamic library (DEDL) (this work): an anchor DNA forms dynamic duplexes with multiple ligand DNA strands, forming the library. Adding the target shifts the equilibrium, favouring the formation of high affinity binders. A photo-crosslinker in the anchor DNA locks the shifted equilibrium under irradiation. Crosslinked binders can then be isolated for hit identification via PCR amplification and DNA sequencing.
