Genetically encoded, phage-displayed cyclic peptide library and methods of making the same

A method of selecting cyclic peptides that bind to a desired target, said method comprising:

• (a) transforming a phage display library comprising a plurality of nucleic acids into bacterial host cells,
• wherein the nucleic acids comprise phage coat protein genes comprising a combinatorial region, and
• wherein the combinatorial region encodes at least one cysteine and at least one non-canonical amino acid;
• (b) expressing the phage coat protein genes within the bacterial host cells,
• wherein the bacterial host cells produce phage particles from the nucleic acids,
• wherein the phage particles contain phage coat proteins with the at least one cysteine and the at least one non-canonical amino acid in the combinatorial region, and
• wherein the at least one cysteine and the at least one non-canonical amino acid couple to one another to form a cyclic peptide;
• (c) screening the phage particles against the desired target,
• wherein the screening results in the selection of phage particles with cyclic peptides that bind to the desired target;
• and
• (d) identifying the amino acid sequences of the cyclic peptides of the selected phage particles.