Synthesis and applications for unnatural sugar nucleotides

The synthesis and biological evaluation of carbohydrate mimetics has begun to more clearly define the diverse roles of carbohydrates in nature. Often the strategy invoves the design and synthesis of glycosyltransferase and glycosidase inhibitors both as tools to elucidate the mechanism of action of these enzymes and as potential therapeutic agents. An array of unnatural sugar nucleotides have found utility in chemo-enzymatic synthesis. The regio- and stereoselective transfer of sugars by glycosyltransferases such as b1,4-galactosyltransferase, a1,3-fucosyltransferase, a2,3- and a2, 6-sialyltransferases and N-acethylglucosaminyltransferase V has demonstrated the broad application of this approach. This review summarizes the specificity of these well-studied glycosyltransferases for both unnatural sugar donors and acceptors. This information combined with the knowledge of the mechanism of action of those enzymes is valuable in the design of potent selective glycosyltransferase inhibitors and the chemo-enzymatic synthesis of novel carbohydrate mimetics.