Synthesis of Glycoconjugates

The synthesis of glycoconjugates opens the route to one of the most important class of biomolecules which play an active role in relevant biological reactions [26]. One way to do so is to use enzymes, which, however, suffer from instability and slow reaction rates. 

Pozsgay, V. (1998) Synthesis of glycoconjugate vaccines against Shigella dysenteriae type 1. J. Org. Chem. 63, 5983-5999. 

The high specificity and stereoselectivity of enzymes, as well as the mild conditions under which they react, make enzyme-catalyzed reactions versatile tools in the synthesis of glycoconjugates. In some instances, an enzymic one-step transformation affords higher yields then the conventional and more-complex chemical synthesis. The application of enzymes in glycopeptide synthesis is under active development for selective deprotection and glycosylation purposes. 

Figure 5.1 General approach for the synthesis of glycoconjugates by multi-enzyme systems.

In the following sections we summarize multi-enzyme systems for the synthesis of glycoconjugates (Table 5.1) following the general scheme for the combination of enzyme modules (see Figure 5.1). Many of these multi-enzyme systems have been already reviewed - here we will highlight those which have been recently been developed. 

On the other hand, the enzymatic synthesis of glycoconjugates and oligosaccharides leads to high product yields in a short time by stereo- and regioselective one-step reactions. All enzymatic reactions are easy to scale up and are carried out in aqueous media under mild conditions. A whole set of enzymes is now available to build up OAT bonds in monosaccharides, COP bonds in activated monosaccharides e.g. phosphorylated sugars or nucleotide sugars, and C-O-C bonds in di- and oligosaccharides (Fig. 1). However, all these enzymatic reactions are limited by the substrate spectrum of the individual enzyme. 

Primary and secondary nucleotide sugars are needed for the preparative synthesis of glycoconjugates with glycosyltransferases. Enzymes for the formation... 

In summary, many important in situ regeneration cycles for nucleotide sugars have been established for the synthesis of glycoconjugates with glycosyl-transferases. However, more detailed investigations will be needed to define the inhibition, the stability and the kinetics of the enzymes involved, and to achieve synthesis conditions with high yields and high enzyme productivities. 

Wu, X. and Bundle, D.R. (2005) Synthesis of glycoconjugate vaccines for Candida albicans using novel linker methodology. Journal of Organic Chemistry, 70, 7381-7388. 

Li J, Robertson DE, Short JM, Wang PG. Chemical and enzymatic synthesis of glycoconjugates. 5 one-pot regioselective synthesis of bioactive galactobiosides using a CLONEZYME thermophilic glycosidase library. Bioorg. Med. Chem. Lett. 1999 9 35-38. 

Schmidt, R R, Recent developments in the synthesis of glycoconjugates. Pure Appl. Chem., 61, 1257-1270, 1989. 

Combinatorial Synthesis of Glycoconjugates for Elucidation of Immunobiological Function... 

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