Isolation of High‐Affinity Trypsin Inhibitors from a DNA‐Encoded Chemical Library

Maturing is easy to do: Annealing benzamidine–oligonucleotide conjugates with a library of DNA-encoded compounds allows the affinity capture of pharmacophores that are capable of binding to exosites adjacent to the primary substrate-binding pocket of the serine protease trypsin. Selected conjugates show an improvement in IC50 values of several orders of magnitude compared with the starting benzamidine.