Nucleotide activated donor sugars

Table 1. Useful protocols for the synthesis of nucleotide-activated donor sugars ...

In comparison with the fully chemical synthesis of nucleotide-activated donor sugars the chemo-enzymatic or enzymatic approaches are distinguished by fewer protecting group manipulations and high chemo- and stereoselectivity. This simplifies purification protocols significantly. These features reduce the number of synthetic steps and increase overall yields. 

In mammalian systems, the Leloir-transferases play the central role in the biosynthesis of glycosidic bonds [33]. These enzymes transfer a monosaccharide unit from a nucleotide activated donor regio- and stereoselectively onto a specific OH-group of an acceptor sugar (Fig. 1). 

The most frequently applied concepts for the enzymatic formation of oligosaccharides and glycoproteins involve the utilization of glycosyl transferases or exo- and e do-glycosyl hydrolases (glycosidases) [58]. Glycosyl transferases require expensive and often unstable sugar nucleotides as activated donor substrates, a major problem besides the poor availability of the enzymes. However, trans-... 

In this context, the use of enzymes has emerged as a practical alternative to chemical synthesis [6-13]. Several examples have been reported that are based on the use of Leloir type-glycosyltransferases, which are mostly membrane-associated and act on nucleotide-activated sugars as donor substrates. However, the use of these enzymes in vitro still remains limited by the difficulty of enzyme purification and by their need for expensive sugar-nucleotides [6]. Re-engineering of microbial cells producing these proteins appears to be promising for the synthesis of specific carbohydrate stmctures [14]. 

Leloir-GTs utilize sugar nucleotides as activated donor substrates. Sugar moieties bound to nucleoside mono- or diphosphates, like cytosine monophosphate (CMP), thymidine diphosphate (dTDP), guanosine diphosphate (GDP), and the most common uridine diphosphate (UDP), are transferred by two types of Leloir-GTs. 

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