Solid-phase synthesis of human salivary mucin-derived O-linked glycopeptides

Short glycopeptides derived from salivary mucin have been synthesized in order to delineate the O-glycosylation pattern that is important in the biological activity of mucin. Two glycopeptides, APPETT*AAP-OMe and PAPPSS*SAP-OMe (* = α-D-GalNAc), were prepared by solid-phase peptide synthesis integrating the Fmoc and Boc strategies. Since these peptides contain a C-terminal proline, we devised an efficient strategy using facile Boc chemistry, where the glycosylation at the desired position in the sequence was achieved using corresponding Fmoc-glycoamino acid esters A and B as building blocks. The transformation of the 2-azido group into the acetamido derivative was performed with thioacetic acid on the polymer-bound glycopeptides. Corresponding nonglycosylated peptides were also synthesized to study the influence of α-D-GalNAc on peptide backbone conformation.