Systematic synthesis of sulfated sialyl-alpha-(2 --> 3)-neolactotetraose derivatives and their acceptor specificity for an alpha-(1 --> 3)-fucosyltransferase (Fuc-TVII) involved in the biosynthesis of L-selectin ligand.
Sulfated sialyl-alpha-(2 --> 3)-neolactotetraose (IV3NeuAcnLcOse4) derivatives at C-6 of GlcNAc (6-O-sulfo), terminal Gal (6'-O-sulfo), and both GlcNAc and Gal (6,6'-di-O-sulfo) residues have systematically been synthesized. (Methyl 5-acetamido-4,7,8,9- tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosy lonate)-(2 --> 3)-2,4-di-O-benzoyl-6-O-levulinoyl-D-galactopyranosyl trichloroacetimidate was coupled with 2-(trimethylsilyl)ethyl (2-acetamido-2-deoxy- 3-O-benzyl-6-O-p-methoxyphenyl-beta-D-glucopyranosyl)-(1 --> 3)-(2,4,6-tri-O-benzyl-beta-D-galactopyranosyl)-(1 --> 4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside to give the suitably protected pentasaccharide which, upon selective removal of the p-methoxyphenyl and/or levulinoyl groups at C-6 of the GlcNAc and the terminal Gal residues, successive O-sulfation(s) and deprotection, afforded the desired three sulfated IV3NeuAcnLcOse4 derivatives. Acceptor specificity of the synthetic IV3NeuAcnLcOse4 probes for a human alpha-(1 --> 3)-fucosyltransferase (Fuc-TVII) was examined to study the biosynthetic pathway of L-selectin ligand. Only the 6-sulfated derivative at C-6 of GlcNAc was recognized by Fuc-TVII to give 6-O-sulfo sialyl LeX.
Fukunaga
K
K
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Shinoda
K
K
Ishida
H
H
Kiso
M
M
D001667:Binding, Competitive; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000096:biosynthesis; D005647:Fucosyltransferases / Q000378:metabolism*; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis*; D008024:Ligands; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis* / Q000378:metabolism*
D002241:Carbohydrates; D008024:Ligands; D009844:Oligosaccharides; D011994:Recombinant Proteins; D013463:Sulfuric Acid Esters; D019041:L-Selectin; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase