Peptide Thioester Formation by an N to S Acyl Shift Reaction at the Cysteinyl Prolyl Cysteine Position

In protein synthesis, peptide thioesters are frequently used as key building blocks for the ligation strategy. We report herein on the synthesis of a peptide thioester using an N to S acyl shift reaction. A peptide containing a Cys-Pro-Cys (CPC) sequence was transformed into a peptide diketopiperazine (DKP) thioester under acidic conditions. In this reaction, the CPC moiety undergoes a tandem N to S acyl shift, followed by DKP formation to give the desired thioester. Since proteins containing a CPC sequence can be prepared by recombinant DNA techniques, the CPC peptide represents a new method for preparing peptide thioesters as recombinant proteins for protein synthesis.