Peptide αthioester formation using standard Fmoc-chemistry

A highly efficient and simple Fmoc-based preparation of peptide (alpha)thioesters is presented. After Fmoc/t-butyl solid-phase synthesis on 2-chlorotrityl resin the C-terminal carboxylic group of the protected peptide is directly converted to the corresponding thioester. The method leads to very high yields, shows a low level of epimerization and can be easily applied also for the preparation of long peptide (alpha)thioesters as demonstrated for the 41 amino acid N-terminal fragment of pro-neuropeptide Y (proNPY 1-40). (C) 2003 Elsevier Science Ltd. All rights reserved.