Chromatographic separation of Lewis a and Lewis x oligosaccharides as glycosynthons

摘要

Lewis a and Lewis x oligosaccharides Galβ3(Fucα4)GlcNAcβ3Galβ4Glc and Galβ4(Fucα3)GlcNAcβ3Galβ4Glc are easily isolated as a mixture from biological fluids, including human milk. However, because they behave almost identically in most Chromatographic systems, it is difficult to have each of them as a pure compound. Incidentally, we found that they were easily separated by HPLC as glycosynthons [Galβ3(Fucα4)GlcNAcβ3Galβ4Glc-Glp-βAla-OBzl and Galβ4(Fucα3)GlcNAcβ3Galβ4Glc-Glp-βAla-OBzl] after substitution of the terminal reducing sugar by a short peptide (pyroglutamyl-βalanyl-O-benzyl ester) in a one-pot two-step reaction (Carbohydr. Lett. 1 (1995) 269; Bioconjug. Chem. 9 (1998) 268). Such glycosynthons are easily either converted back to native Lewis a and Lewis x oligosaccharides upon hydrazinolysis or used to synthesize glycoconjugates, such as glycoclusters, glycopeptides, glycooligonucleotides, glycosylated polymers or glycosylated matrices for therapeutic or analytical purposes.