Synthesis and selectin-binding activity of N-deacetylsialyl Lewis X ganglioside.
A novel analogue of sialyl Lewis X ganglioside, N-deacetylsialyl Lewis X ganglioside, was synthesized. Methyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-5-trifluoroacetamido-D-glycero-alpha-D-galacto-2-nonulopyranosylonate-(2 --> 3)-2,4,6-tri-O-benzoyl-D-galactopyranosyl trichloroacetimidate was coupled with 2-(trimethylsilyl)ethyl [2-acetamido-6-O-benzyl-2-deoxy-3-O-(4-methoxybenzyl)-beta-D-glucopyranosyl]-(1 --> 3)-[2,4,6-tri-O-benzyl-beta-D-galactopyranosyl]-(1 --> 4)-2,3,6-tri-O-benzyl-beta-D-galactopyranoside to give the desired pentasaccharide in high yield. The glycosylation of the pentasaccharide acceptor, which was derived from its precursor by removal of the 3-methoxybenzyl group, with the phenyl 1-thioglycoside derivative of L-fucose using N-iodosuccinimide-trifluoromethanesulfonic acid as promoter, produced the hexasaccharide. Proper manipulation of the protecting groups of the hexasaccharide afforded the corresponding glycosyl imidate, which was coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol. Selective reduction of the azido group, N-acylation with octadecanoic acid, and the complete removal of the protecting groups gave the desired N-deacetylsialyl Lewis X ganglioside. L-Selectin bound more strongly to N-deacetylsialyl Lewis X ganglioside than to the sialyl Lewis X ganglioside, whereas E- and P-selectins bound equally well to the two gangliosides.
Yamaguchi
Masanori
M
Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193, Japan.
Ishida
Hideharu
H
Galustian
Christine
C
Feizi
Ten
T
Kiso
Makoto
M
D019040:E-Selectin / Q000737:chemistry; D005732:Gangliosides / Q000138:chemical synthesis / Q000737:chemistry*; D006031:Glycosylation; D019007:P-Selectin / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D019087:Selectins / Q000737:chemistry*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives
D019040:E-Selectin; D005732:Gangliosides; C475345:N-deacetylsialyl Lewis X ganglioside; D019007:P-Selectin; D011994:Recombinant Proteins; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside