Schematic depiction of the RaPID selection of macrocyclic peptides against FXIIa. Translation of an mRNA library under a reprogrammed genetic code gives a macrocyclic peptide library containing (1S,2S)-2-ACHC, (1S,2S)-2-ACPC, and (1R,2R)-2-ACPC conjugated with mRNA via a puromycin linker. After the reverse transcription of mRNA into cDNA, the peptide/mRNA/cDNA conjugates are subjected to binding selection against FXIIa immobilized on magnetic beads. Then, cDNAs are recovered and amplified into a cDNA library followed by transcription into an mRNA library. By repeating this selection cycle for several rounds, strong FXIIa binders can be obtained.