Glycopeptide Synthesis Based on a TFA-Labile Protection Strategy and One-Pot Four-Segment Ligation for the Synthesis of O-Glycosylated Histone H2A

This paper describes the chemical synthesis of O-glycosylated protein, histone H2A, using the trifluoroacetic acid (TFA)-labile protection strategy for sugar alcohols in the preparation of the glycosylated peptide segment and the one-pot four-peptide-segment native chemical ligation (NCL) using a peptide thioester and two orthogonal thioester equivalents. Using these key methods, the entire sequence of H2A carrying O-(N-acetylglucosamine) at Ser([40]) was successfully obtained in a high overall yield.