Synthesis of Heavily Glycosylated Peptide αThioester

Erythropoietin (EPO) needs to be heavily glycosylated to exhibit its bioactivity in vivo. In order to synthesize heavily glycosylated EPO analogues, corresponding glycosylated peptide ^αthioesters are essential to prepare glycosylated whole EPO peptide backbones through native chemical ligation. After construction of the peptide ^αthioester corresponding to the 1–32 amino acid sequence in EPO, we aimed to incorporate three complex-type biantennary sialyloligosaccharides to this peptide ^αthioester by the haloacetamide method. The reaction afforded the desired heavily glycosylated peptide ^αthioester.