Syntheses of alpha-dystroglycan derived glycosyl amino acids carrying a novel mannosyl serine/threonine linkage

alpha -Dystroglycan (alpha -DG) is a membrane-associated, extracellular gly coprotein. It is anchored to the cell-membrane by binding to the transmembr ane glycoprotein beta -dystroglycan (beta -DG) to form an alpha/beta -DG-co mplex. It was discovered that the bovine peripheral nerve alpha -DG possess es the Ser/Thr linked tetrasaccharide as the major constituent of the O-lin ked carbohydrates, which was proposed to contribute laminin binding activit y of this glycoprotein. This structure has a striking feature in terms of the mode of linkage betwe en oligosaccharide and the core protein. It has a mannose residue linked to the core protein through Ser/Thr residue. A similar structure was proposed to exist in brain derived HNK-1 immunoreactive O-glycans. Being interested in the structural novelty and potential biological significance of this ty pe of glycan chains, the chemical synthesis of Ser/Thr linked mannose conta ining tetrasaccharide was investigated. Tetrasaccharide donor was construct ed from monosaccharide blocks and coupled with Ser/Thr derivatives. Subsequ ent deprotection afforded target tetraosyl serine. Furthermore, synthetic r outes to lower homologues, namely Gal-beta-(1,4)-GlcNAc-beta-(1,2)-Man-alph a -Ser and GlcNAc-beta-(1,2)-Man-alpha -Ser were also provided.