Aspartyl methyl ester formation via aspartimide ring opening: a proposed modification of the protocols used in Boc- and Fmoc-based solid-phase peptide synthesis

Aspartimide formation is still an unresolved problem in the solid-phase peptide synthesis of aspartic acid-containing peptides, following either Boc- or Fmoc-based synthetic strategies. α-Aspartyl peptides of high purity can be obtained, despite aspartimide formation, by incorporating an additional step in the Boc- and Fmoc-based solid-phase peptide synthesis protocols, consisting of treatment of the peptide-resin with methanol in the presence of 2% DIEA (v/v) for 15 min immediately after completion of the peptide chain elongation.