Relative configuration of Cys-Pro ester peptides in thioester formation

A peptide containing a cysteinyl prolyl ester (CPE) moiety at the C-terminus (CPE peptide) was transformed into a diketopiperazine (DKP) thioester via an intramolecular N-S acyl shift reaction and was then used for peptide ligation. The difference in reactivity between the CPE peptide stereoisomers was examined. In reactions of the CPE peptides that contained L-Cys-L-Pro or D-Cys-D-Pro, the desired DKP thioester was formed at the preceding amino acid residue. On the other hand, in reactions of the CPE peptides that contained D-Cys-L-Pro or L-Cys-D-Pro, a thiolactone was formed at the C-terminal prolyl ester, and the ligation occurred at the C-terminal Pro residue. Using this reaction, it was possible to efficiently prepare a cyclic peptide.