Chemoenzymatic Synthesis of Linear- and Head-to-Tail Cyclic Peptides Using Omniligase-1

Omniligase-1-catalyzed ligation represents a powerful tool for the efficient intermolecular and intramolecular (head-to-tail cyclization) ligation of peptides. Reactions are irreversible and proceed with unprotected peptides (μM-mM concentration) in aqueous solution at slightly basic pH. Due to its high catalytic efficiency, only very low molar equivalents of omniligase-1 are required. In this chapter, a chemoenzymatic peptide synthesis (CEPS) approach for the assembly of medium-to-long-sized linear peptides as well as for efficient peptide head-to-tail cyclization is described. In particular, we provide protocols for the chemoenzymatic synthesis of the peptide therapeutic exenatide, a GLP-1 (glucagon-like peptide) analogue, and the macrocyclization and oxidative folding of the cyclotide MCoTI-II in a one-pot procedure.