Synthesis of Unprotected Linear or Cyclic O-Acyl Isopeptides in Water Using Bis(2-sulfanylethyl)amido Peptide Ligation.

SEA ligation proceeds chemoselectively at pH 3, i.e., at a pH where the O-acyl isopeptides are protected by protonation. This property was used for synthesizing unprotected O-acyl isopeptides in water, starting from peptide segments which are easily accessible by the Fmoc SPPS.