Fmoc-Compatible Solid-Phase Peptide Synthesis of Long C-Terminal Peptide Thioesters

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

“…13 A number of synthetic methods for preparing peptide thioesters based on the Fmoc SPPS procedure have been reported. These methods include the use of a Wang linker, which is replaced by a thiol, 14 an aryl hydrazine linker, 15 an in situ O to S acyl shift reaction, 16 trithioortho esters, 17 and an O-aminoanilide moiety, which is activated to give the N-acylurea, and thiolysis to give a thioester. 18 Each method may overcome some of the difficulties associated with peptide thioester synthesis by the Fmoc SPPS procedure.…”

Synthesis of Proteins by Native Chemical Ligation Using Fmoc‐Based Chemistry

“…acid long N-terminal fragment of the bovine pancreatic trypsin inhibitor [44]. This fragment was obtained in overall 8% yield, which can be compared with the 15% yield for the same peptide obtained by the Boc method.…”

“…However, some problems arising from epimerization of C-terminal residues other than Gly and undesired reactions, especially formation of side chain thioesters and aspartimide rearrangement, were also observed [43]. Further studies have shown that by using AlMe 3 in place of the more acidic AlMeCl 2 , the formation of aspartimides and aspartic acid side chain thioesters can be greatly suppressed [25,44]. However, although AlMe 3 has been shown to be compatible with peptides of complex composition, earlier studies have suggested that the extent of epimerization of susceptible C-terminal thioesters would also increase.…”

Chapter 2 Protein Engineering with the Traceless Staudinger Ligation

“…The C-terminus is then activated ( e.g. , with DCC, PyBOP, or NHS) and coupled with phosphinothiol I .A peptide fragment is assembled by standard Fmoc chemistry on a 4-hydroxymethylphenylacetamidomethyl (PAM) or 4-hydroxymethylbenzoic acid (HMBA) resin (Sewing & Hilvert, 2001). The ester linkage is activated for cleavage by AlMe 3 in the presence of an excess of phosphinothiol I .…”