ENZYMATIC AND CHEMOENZYMATIC SYNTHESIS OF CARBOHYDRATES

Carbohydrate-mediated biochemical recognition processes are potential targets for drug development. The synthesis of complex carbohydrates and related structures, however, has been a difficult task, especially from practical point of view. New solution- and solid-phase methods based on enzymatic and a combined enzymatic and chemical procedure have recently been developed for the practical synthesis of various carbohydrate-related structures. Monosaccharides, aza- and thiosugars, and their analogs can be effectively prepared based on aldolase-catalyzed reactions. Many oligosaccharides can now be synthesized on multi-gram or kilogram scales based on recombinant glycosyltransferases with in situ regeneration of sugar nucleotides. Serine proteases can be engineered to peptide ligases for glycopeptide coupling in aqueous solution, and further enzymatic incorporation of sugars to form complex glycopeptides can be achieved. Phospholipids containing sugars and azasugars can be prepared using phospholipase D-catalyzed exchange reaction followed by self-assembly to form liposome-like structures with sugars displayed on the surface. These newly developed chemo-enzymatic methods have been applied to the synthesis of specific inhibitors of glycosidases and glycosyltransferases, and of receptors of carbohydrate-mediated cell adhesion.