Figure 1.

General scheme for affinity selection of macrocyclic peptides from ribosomally synthesized libraries. A DNA library (left) is translated in such a way as to produce a link between each peptide and its cognate DNA, and is cyclized (often through reactions involving Cys residues and leading to formation of thioethers) to produce a DNA–peptide library. This is panned against a surface-immobilized target protein. A DNA library enriched for sequences encoding peptides that bind to the target is recovered and can be used for iterative rounds of selection or can be sequenced to determine the sequences of the peptides with a target affinity.