Macrocyclic DNA-encoded chemical libraries: a historical perspective.

While macrocyclic peptides are extensively researched for therapeutically relevant protein targets, DNA-encoded chemical libraries (DELs) are developed at a quick pace to discover novel small molecule binders. The combination of both fields has been explored since 2004 and the number of macrocyclic peptide DELs is steadily increasing. Macrocycles with high affinity and potency were identified for diverse classes of proteins, revealing DEL's huge potential. By giving a historical perspective, we would like to review the methods which permitted the rise of macrocyclic peptide DELs, describe the different DELs which were created and discuss the achievements and challenges of this emerging field.