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

Abstract

Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.