1-N-Glycyl .beta.-oligosaccharide derivatives as stable intermediates for the formation of glycoconjugate probes

• Published in: Biochemistry (Easton) 1992-11, Vol.31 (44), p.10724-10732
• Main Authors: Manger, I. D, Rademacher, T. W, Dwek, R. A
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - chemistry; Acylation; Analytical biochemistry: general aspects, technics, instrumentation; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Carbohydrate Conformation; Carbohydrate Sequence; Chromatography, High Pressure Liquid; Dansyl Compounds - chemistry; Fluoresceins - chemistry; Fundamental and applied biological sciences. Psychology; Glycoconjugates - chemical synthesis; Glycoconjugates - chemistry; Glycosylation; Humans; Magnetic Resonance Spectroscopy; Molecular Sequence Data; Oligosaccharides - chemical synthesis; Oligosaccharides - chemistry; Swine
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi00159a012

Incubation of reducing sugars in ammonium bicarbonate was found to be a simple procedure for the formation of beta-D-glycosylamines of purified complex oligosaccharides in 70-80% yield. These provide valuable intermediates for the synthesis of a wide range of oligosaccharide probes and derivatives by acylation of the 1-amino function. The 1-amino function showed different rates of reactivity with different reagents. In general, interactions with large ring systems such as the fluorophores dansyl chloride and carboxyfluorescein gave 10-20% yields of products, which consisted of mixtures of both anomeric forms, whereas smaller acylating reagents gave near-quantitative yields of the desired beta-D-derivatives. Steric effects may explain differences in reactivity. N-Chloroacetamido derivatives could be obtained in high yield with retention of the beta-anomeric configuration. Subsequent ammonolysis of the chloroacetamido function afforded the corresponding N-glycyl beta-derivatives. The linker thereby introduced retains the amino function, possesses the useful properties of fixed anomeric configuration, improved stability, and uniform reactivity with a variety of reagents, and is structurally analogous to an asparagine side chain. The potential therefore exists for the generation of oligosaccharide derivatives tailored for different applications.