2-Cyanopyrimidine-Containing Molecules for N-Terminal Selective Cyclization of Phage-Displayed Peptides.

Current methods for the macrocyclization of phage-displayed peptides often rely on small molecule linkers that nonspecifically react with targeted amino acid residues. To expand tool kits for more regioselective macrocyclization of phage-displayed peptides, this study explores the unique condensation reaction between an N-terminal cysteine and nitrile along with the reactivity of an internal cysteine. Five 2-cyanopyrimidine derivatives were synthesized for this purpose and evaluated for their selective macrocyclization of a protein-fused model peptide.