Chemoenzymatic Synthesis of Glycans : Overview

Abstract

The synthesis of glycans has a long history, and its advancement continues to evolve along with the methods available for the analysis of glycans (see reviews Hsu et al. 2011; Paulsen 1982; Schmidt et al. 1999). This chapter covers various aspects of methodology development, including the development of glycosylation reagents and protecting groups, and programmable one-pot synthesis (Zhang et al. 1999) as well as automated solid-phase synthesis of oligosaccharides (Plante et al. 2001). The use of enzymes in the synthesis of complex glycans has not been fully appreciated until in the 1980s when glycosyltransferases were shown to be useful for the synthesis of glycans if coupled with regeneration of sugar nucleotides (Wong et al. 1982). Since then, various strategies and methods have been further developed to improve the methodology (Hsu et al. 2011; Wang et al. 2013), including enzyme expression and its improvement with directed evolution and reactor configuration. With regard to reactor configuration, the enzymes could be used as free forms in a homogeneous system or immobilized to beads or solid supports or polymers in order to recover the enzymes for reuse. In general, the use of free enzymes in a homogeneous system has been most common and practical and could be carried out in a one-pot manner for the gram-scale or kilogram-scale synthesis of oligosaccharides such as sialyl Lewis x tetrasaccharide (Ichikawa et al. 1992) and Globo H or SSEA4 hexasaccharide (Tsai et al. 2013).