Sialosides, enzymatic preparation

Figure 4. Enzymatic Preparation of O-linked sialosides. Adapted from reference...

The total synthesis of sialosides by using the chemoenzymatic approach is as follows [74]. Sialic acid itself can be synthesized from ManNAc, mannose, or their derivatives by sialic acid aldolase enzyme through aldol condensation reaction. If ManNAc is chemically or enzymatically modified at C2, C4—C6 positions, sialic acid has structural modifications at C5, C7-C9 positions, respectively. The sialic acids are subsequently activated by a CMP-siahc acid synthetase to form a CMP-sialic acid, which is the donor used by sialyltransferases. Because CMP-sialic acid is tmstable, the CMP-Neu5Ac synthetase is valuable for the preparative enzymatic synthesis of sialosides. In the last steps, the CMP-sialic acid is transferred to galactose or GalNAc terminated glycosides by sialyltransferases to form structurally defined sialosides. Examples are that Chen and co-workers have recently developed a one-pot multienzyme system for the efficient synthesis of a-sialosides (Table 2) [12,76,79]. In this system, recombinant E. coli K-12 sialic acid aldolase catalyzed the synthesis of sialic acid precursors for... 

Cell-surface sialic acid residues play important roles in diverse biological processes [86]. Sialic acids are usually found in terminal positions linked through an a-glyco-sidic linkage. The stereoselective synthesis of a-sialosides remains a challenge because the glycosides have the thermodynamically unfavorable equatorial orientation and the anomeric carbon is a very hindered quaternary center [4]. Enzymatic sialylation is, therefore, an attractive alternative means of preparation of a-sialosides in an efficient and stereocontrolled manner. 

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