Syntheses of alpha-dystroglycan derived glycosyl amino acids carrying a novel mannosyl serine/threonine linkage.
Alpha-dystroglycan (alpha-DG) is a membrane-associated, extracellular glycoprotein. It is anchored to the cell-membrane by binding to the transmembrane glycoprotein beta-dystroglycan (beta-DG) to form an alpha/beta-DG-complex. It was discovered that the bovine peripheral nerve alpha-DG possesses the Ser/Thr linked tetrasaccharide as the major constituent of the O-linked carbohydrates, which was proposed to contribute laminin binding activity of this glycoprotein. This structure has a striking feature in terms of the mode of linkage between 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 type of glycan chains, the chemical synthesis of Ser/Thr linked mannose containing tetrasaccharide was investigated. Tetrasaccharide donor was constructed from monosaccharide blocks and coupled with Ser/Thr derivatives. Subsequent deprotection afforded target tetraosyl serine. Furthermore, synthetic routes to lower homologues, namely Gal-beta-(1,4)-GlcNAc-beta-(1,2)-Man-alpha-Ser and GlcNAc-beta-(1,2)-Man-alpha-Ser were also provided.
Seifert
J
J
RIKEN (The Institute of Physical and Chemical Research), Wako-shi, Saitama, Japan.
Ogawa
T
T
Kurono
S
S
Ito
Y
Y
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D003598:Cytoskeletal Proteins / Q000138:chemical synthesis* / Q000737:chemistry*; D049030:Dystroglycans; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000138:chemical synthesis* / Q000737:chemistry*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry; D010525:Peripheral Nerves / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013912:Threonine / Q000737:chemistry
D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D049030:Dystroglycans; D013912:Threonine; D012694:Serine; D008358:Mannose