Preparation of thioesters for the ligation of peptides with non-native substrates

A one-pot procedure for the synthesis of thioesters from primary amines is reported. Polyamides containing one or more primary amines were prepared by solid-phase synthesis and reacted with thiolane-2,5-dione followed by alky lation with benzyl bromide to produce the target thioesters in good yield. The thioesters thus prepared were conjugated to peptides to produce polyami de-peptide chimeras using the 'native chemical ligation' method. This flexi ble synthetic procedure provides a ready route to both natural and unnatura l substrates for chemical ligation reactions. (C) 2000 Elsevier Science Ltd . All rights reserved.