Omniligase-1 mediated peptide cyclization for phage display

We report an enzymatic cyclization strategy, termed omniligase-1 mediated peptide bicyclization. Electrophilic group was introduced into the recognition sequence of omniligase to achieve intramolecular bicyclization with Cys residues. Combined with phage display, we identified a bicyclic peptide ligand targeting TEAD4 with a KD value of 1.5 µM, 100-fold lower than its linear version, demonstrating the utility of this platform for discovering bicyclic peptide ligands.