Metabolic oligosaccharide

Fig. 7. Metabolic oligosaccharide engineering via bioorthogonal Staudinger ligation.

Figure 7 Metabolic oligosaccharide engineering of sialic acid. Exogenously supplied analogs of ManNAc or sialic acid can intercept the sialic acid biosynthetic pathway (at different points) and be displayed on the cell surface in place of the natural sialic acids NeuSAc and Neu5Gc. The sampling of non-natural "R" groups shown here was selected from References 84, 92, 93 and 97-101 (note that not all "mix-and-match" permutations of the indicated groups have been reported). Additional information on the enzymes shown can be found in the KEGG databases (see the Legend for Fig. 3).

The opportunities provided by metabolic oligosaccharide engineering can be divided into two essential classes. First, the intended target glycan can be endowed with a unique function. In particular, ManNAc analogs can be used to increase the repertoire of sialic acids, which is a family of over 50 natural sugars that nature uses to fine-tune function and structure... 

Non-Natural Sugar Analogues Chemical Probes for Metabolic Oligosaccharide Engineering... 

Some early attempts at metabolic oligosaccharide engineering using haloge-nated and deoxy sugars resulted in cell death. In retrospect, we now know that some of these compounds are inhibitory of intracellular biosynthetic pathways [37,38], However, the toxicity of halogenated and deoxy sugars could possibly be exploited therapeutically for antiviral, antibacterial, or anticancer therapy. Examples are presented in detail later in this chapter. 

Metabolic oligosaccharide engineering has also been exploited for the study of PSA. PSA is a linear homopolymer of ct2-8-linked Sia residues that can extend to over 50 residues (Figure 30). PSA is synthesized... 

Dube DH, Bertozzi CR (2003) Metabolic oligosaccharide engineering as a tool for glycobiology. Curr Opin Chem Biol 7 616-625... 

Scheme 16.19 Metabolic oligosaccharide engineering peracetyiated ManNAz 74 is taken up by mammalian cells and converted into an azide-containing sialic acid derivative which is incorporated into sialic acid-bearing glycans 75. in the next step, a detectable probe 76 can be attached to 75 via Staudinger Hgation ...

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