The use of a cysteinyl prolyl ester (CPE) autoactivating unit in peptide ligation reactions

A peptide containing a cysteinyl prolyl ester (CPE) moiety at the C-terminus (CPE peptide) is spontaneously transformed into a diketopiperazine thioester via an intramolecular N-S acyl shift reaction, Followed by diketopiperazine Formation. The CPE peptide can be ligated with a Cys-peptide in a one-pot procedure. The peptide diketopiperazine thioester call also be transformed into a peptide thioester by intermolecular thiol-thioester exchange with external thiol compounds such as sodium mercaptoethanesulfonate. Since CPE peptides call be prepared by standard Fmoc solid-phase synthesis, it is a versatile alternative to the peptide thioester, providing a flexible ligation strategy that promises to be useful in polypeptide synthesis. (C) 2009 Elsevier Ltd. All rights reserved.