Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3-thioGalNAc.
A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. We report here a strategy for the synthesis of O-linked glycopeptide analogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. Higher order oligosaccharides were readily generated by alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars. The rapid assembly of "core 1"and "core 3" O-linked glycopeptide mimetics was accomplished in this fashion.
Marcaurelle
L A
LA
Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.
Bertozzi
C R
CR
D000116:Acetylgalactosamine / Q000737:chemistry*; D000478:Alkylation; D005692:Galactose Oxidase / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis*; D018716:Molecular Mimicry; D009077:Mucins / Q000737:chemistry; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013862:Thiogalactosides / Q000138:chemical synthesis*; D013912:Threonine / Q000737:chemistry
D006020:Glycopeptides; D009077:Mucins; D009844:Oligosaccharides; D013862:Thiogalactosides; D013912:Threonine; D005692:Galactose Oxidase; D000116:Acetylgalactosamine