Peptidyl N-alkylcysteine as a peptide thioester surrogate in the native chemical ligation

Abstract

Peptides having the C-terminal N-alkylcysteine (NAC) with a free carboxy group, which can be easily prepared by the conventional 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS), was directly used for the native chemical ligation (NCL) based on the in situ thioesterification method. The reaction efficiently proceeded under a mild acidic condition (pH ∼5) to give the ligated product. This method was successfully used for the synthesis of the human brain natriuretic peptide, (BNP)-32, showing the usefulness of the peptidyl NAC as a thioester surrogate for the NCL reaction.