Enzymatic On-Resin Peptide Cleavage and in Situ Cyclization One-Pot Strategy for the Synthesis of Cyclopeptide and Cyclotide

A one-pot strategy combining sortase A mediated on-resin peptide cleavage and in situ cyclization was developed for the synthesis of cyclic peptides. This strategy was applied to synthesize head-to-tail cyclic antibacterial bovine lactoferricin peptide LFcinB(20-35) in a yield of 67%. The one-pot strategy was compatible with an oxidative folding reaction, and complex cyclotides containing one or two disulfide bonds, such as sunflower trypsin inhibitors-1 and alpha-conotoxin MII, were successfully synthesized in one pot in a yield of 77% and 61%, respectively.