O-Mannosylated proteins, which contain a covalent linkage between the anomeric position of mannose and a serine or threonine residue, make up approximately 30% of the O-linked glycoproteins in the brain. The attaching mannose may then be extended by the addition of other monosaccharides, in either a linear or branched manner, resulting in the m1, m2, and m3 classes of glycans. O-mannosylation is prevalent in transmembrane proteins, and is important in modulating cell-matrix interactions, cell adhesion, and cell-cell signaling. Disruption of O-mannose glycosylation often results in various congenital muscular dystrophies termed dystroglycanopathies. A recently characterized class of O-mannosylated glycans is the m3 structure, which contains at its terminus an alternating Xyl-GlcA repeat unit. This tandem unit functions as a scaffold for the formation of the ligand binding moiety of alpha-dystroglycan, a well characterized mammalian mannosylated protein. The biological importance of glycosylation is well known, but poorly understood due to the variability and heterogeneity of polysaccharides in biological systems. Therefore, the synthesis of these glycans will help obtain pure, measurable quantities of different glycan structures to be used in biological and biochemical studies. A synthesis of the Xyl and GlcA monosaccharide building blocks and their incorporation into the Xyl-GlcA repeat will be presented. In addition, the automated solution phase synthesis of several m1 and m2 glycans will be presented.

Synthesis of the Xyl-GlcA disaccharide repeat of the m3 O-mannosylated glycan

255th National Meeting (2018)

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