Chemoselective elaboration of O-linked glycopeptide mimetics by alkylationof 3-ThioGalNAc

A critical branch point in mucin-type oligosaccharides is the beta1 --> 3 g lycosidic linkage to the core alpha -N-acetylgalactosamine (GalNAc) residue . We report here a strategy for the synthesis of O-linked glycopeptide anal ogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. The key building block was a 2-azido-3-thiogala ctose-Thr analogue that was incorporated into a peptide by fluorenylmethoxy carbonyl (Fmoc)-based solid-phase peptide synthesis. Higher order oligosacc harides were readily generated by alkylation of the corresponding 3-thioGal NAc with N-bromoacetamido sugars. The rapid assembly of "core 1" and "core 3" O-linked glycopeptide mimetics was accomplished in this fashion.