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Biological Chemistry

Easy Route To Sugar Building Blocks

Carbohydrates: Simple method could ease preparation of oligosaccharides

by Stu Borman
October 22, 2012 | A version of this story appeared in Volume 90, Issue 43

Imidazole-based reagent sparks addition of sugar phosphates and nucleoside phosphates, yielding sugar-NDPs in aqueous solution.
This scheme shows how sugar-NDP is formed.
Imidazole-based reagent sparks addition of sugar phosphates and nucleoside phosphates, yielding sugar-NDPs in aqueous solution.

A new method easily yields sugar nucleoside diphosphates (sugar-NDPs), which are required starting materials for chemoenzymatic oligosaccharide synthesis. If the method proves applicable for a wide variety of sugars, it could ease oligosaccharide synthesis for drug discovery and biological studies. Oligo­saccharides, or glycans, play key biological roles in immunity, blood type, molecular recognition, and cell signaling.

Postdoc Hidenori Tanaka, carbohydrate chemist Ole Hindsgaul, and coworkers at Carlsberg Laboratory, in Copenhagen, developed the technique and tested it on three sugars(Angew. Chem. Int. Ed., DOI: 10.1002/anie.201205433). Hindsgaul says he devised the route “to get people out of my hair, writing and asking if we can make this or that sugar-NDP for them.”

Most methods for combining a sugar and a nucleotide into a sugar-NDP are difficult and inconvenient. They require anhydrous organic solvents, products must be isolated prior to further synthetic manipulation, protecting groups are often required, and the procedures are notoriously irreproducible.

Hindsgaul’s one-pot strategy, however, takes place in water, doesn’t require protecting groups, is reproducible, and has respectable yields (about 50%). The method uses 2-imidazolyl-1,3-dimethylimidazolinium chloride to activate the reaction between sugar phosphates and nucleotide phosphates to form sugar-NDPs.

Product mixtures can be used directly, without isolation or solvent cleanup, as sugar-donor sources for glycosyltransferase-catalyzed glycan synthesis. Researchers “can simply add compounds in sequence, and out pops the sugar-NDP in a solution that can be directly added to a glycosyltransferase and acceptor [sugar] in buffer,” Hindsgaul says.

“There has been no general method for chemical sugar-NDP synthesis that works reproducibly for all sugars in an easy manner and across different labs,” comments glycosyltransferase expert Gerd Wagner of King’s College London, who uses sugar-NDPs extensively in his research. “The new reaction certainly has the potential to become such a general method.” What remains to be shown, he says, is whether other labs can reproduce the technique and whether it will be applicable to other natural and nonnatural sugars.



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