Combined chemical and enzymatic synthesis of the sialylated non reducing terminal sequence of GM1b glycolylated ganglioside, a potential human tumor marker.
N-Glycolylglucosamine 8 was synthesized in 4 steps from anisal glucosamine, via the new crystalline monochloracetyl derivatives 3, 4 and 7. N-Glycolylneuraminic acid 10 was prepared in 59% yield starting from pyruvate and a mixture of 8 and its manno epimer 9 in a 2:3 ratio, with immobilized sialic acid aldolase. Neu5Gc 10 was converted into CMP-NeuGc 11 in the presence of immobilized calf brain CMP-sialate synthetase. Finally 11 was used as a donor in the transfer to the acceptor beta-D-Gal-(1-3)-beta-D-GalNAc-OBn 12 catalyzed by a preparation of porcine liver (2-3)-alpha-sialyltransferase, roughly purified by a chromatography on Cibacron Blue-agarose. alpha-Neu5Gc-(2-3)-beta-D-Gal-(1-3)-beta-D-GalNac-OBn 13 isolated in 56% yield was deprotected to give the non-reducing terminal sequence of GM1b glycolylated ganglioside, which might be expressed in human tumors.
Lubineau
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A
Institut de Chimie Moléculaire d'Orsay, URA CNRS 462, Université Paris-Sud, Orsay, France.
Augé
C
C
Gautheron-Le Narvor
C
C
Ginet
J C
JC
D000818:Animals; D014408:Biomarkers, Tumor; D001921:Brain / Q000201:enzymology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002417:Cattle; D002846:Chromatography, Affinity; D004800:Enzymes, Immobilized; D005634:Fructose-Bisphosphate Aldolase; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D007202:Indicators and Reagents; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D000216:N-Acylneuraminate Cytidylyltransferase; D009369:Neoplasms / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D009904:Optical Rotation; D012799:Sialyltransferases / Q000302:isolation & purification; D013552:Swine; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D014408:Biomarkers, Tumor; D004800:Enzymes, Immobilized; D007202:Indicators and Reagents; D009842:Oligopeptides; D005677:G(M1) Ganglioside; C029624:ganglioside M1b; D012799:Sialyltransferases; D000216:N-Acylneuraminate Cytidylyltransferase; D005634:Fructose-Bisphosphate Aldolase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase