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

Abstract

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 alkylation with benzyl bromide to produce the target thioesters in good yield. The thioesters thus prepared were conjugated to peptides to produce polyamide–peptide chimeras using the 'native chemical ligation' method. This flexible synthetic procedure provides a ready route to both natural and unnatural substrates for chemical ligation reactions.

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