Glycosidases glycoconjugate synthesis

In order to avoid multi-step chemical syntheses to achieve regio- and stereospecific reactions, glycosidases have been employed as catalysts for glycoconjugate synthesis. Glycosidases are attractive for large-scale application since they are abundant catalysts, inexpensive, commercially available, and exhibit broad processing specificity, particularly with respect to the acceptor, as compared with more substrate specific glycosyltranferases [1]. 

Among the numerous enzymes associated with carbohydrate processing in cells, those used in glycoconjugate synthesis belong to two categories, viz., glycosidases and glycosyltransferases. 

Both transferases from the Leloir and non-Leloir pathways have been employed for the in vitro synthesis of oligosaccharides and glycoconjugates. Glycosidases have also been exploited for synthesis. The function of glycosidases in vivo is to cleave glycosidic bonds,... 

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. 

Fujimoto, H., Isomura, M., and Ajisaka, K. 1996. Synthesis of oligosaccharide components of glycoconjugates using glycosidases. J. Appl. Glycosci. 43 265-272. 

Reversed Hydrolysis vs. Transglycosylation. Glycosidases have been used for several years for the selective hydrolysis of carbohydrates, such as for the hydrolysis of starch and for the analysis of glycoconjugate carbohydrate structures. These enzymes also can be used for the regioselective and stereospecific synthesis of oligosaccharides in equilibrium-controlled (reversed-hydrolysis. Equation 1) or kinetically controlled (transglycosylation. Equation 2) reactions ... 

The problems of low and/or wrong regioselectivity has hindered the application of glycosidases for preparative synthesis of glycoconjugate structures, but, as shown below, these problems have now been largely solved for the synthesis of disaccharides. 

Enzymes have been used extensively to sinq>lify the syndiesis of conq>lex oligosaccharides and glycoconjugates. Glycosyltransferases and glycosidases are valuable catalysts for the formation of specific glycosidic linkages [14,15]. Other enzymes such as aldolases and sulfotransferases can also be exploited for the synthesis of distinct structures that are critical to oligosaccharide functions. 

---