GDP-Fuc

Fucose Deoxyhexose Fuc GDP-Fuc May be external in both N- and 0-linked glycoproteins or internal, linked to the GIcNAc residue attached to Asn in N-linked species. Can also occur internally attached to the OH of Ser (eg, in t-PA and certain clotting factors). 

Scheme 10.1 Glycopeptide synthesis and a-chymotrypsin catalyzed release from the solid support, a) 25% TFA (CH2CI2) b) 0-(N-Boc-Phe)glycolic acid (7 eq), BOP, HOBt, DIEA b) 25% TFA (CH2CI2) c) Boc-Gly-OH (7 eq), BOP, HOBt, DIEA c) 25% TFA (CH2CI2) d) Boc-Asn(GlcNAcb)-OH (3 eq), BOP, DIEA e) galactosyl transferase, sialyl transferase f) CT, H2O, pH 7.0 g) ultrafiltration h) a-l,3-fuco-syltransferase, GDP-Fuc (2.5 eq), 0.1 M HEPES (pH 7.0), 95%.

Various mammalian-tissue preparations were also found224 to catalyze the formation of GDP-Fuc from GDP-Man both NAD+ and an NADPH-generating system were necessary for maximum activity. 

GDP-Fuc From GDP-Man with a crude enzyme preparation from Agrobacterium radiobacter From Fuc-l-P and GTP with GDP-Fuc pyrophosphorylase By chemical synthesis... 

A similar mechanism seems probable for conversion of GDP-6-deoxy-D-(yxo-hexos-4-ulose (7c) into GDP-L-fucose (GDP-Fuc),40,159 although, in this case, the enzymes that participated in the process were not separated, and intermediate formation of the 6-deoxy-L-xy/o-hexosyl-4-ulose derivative (8b) was not demonstrated. 

After incubation of an enzyme preparation from the micro-organism with UDP-Glc and GDP-Fuc, formation of the hexasaccharide derivative 34 was observed.348 It does not correspond in composition to the repeating unit of the polysaccharide, or to its main chain, and further enzymic reactions are necessary in order to complete their assembly. 

Fig. 14. Salvage pathways of nucleotide sugars. L-fucose (11), (3-L-fucose-l-phosphate (12), GDP-p-L-fucose (13), A fucokinase (EC 2.7.1.52), B GDP-Fuc pyrophosphorylase (EC 2.7.7.30). D-galactose (14), a-D-galactose-l-phosphate (15), UDP-a-D-galactose (16), C galactokinase (EC 2.7.1.6), D UDP-Gal pyrophosphorylase. IV-acetyl-D-galactosamine (17), Al-acetyl-a-D-galactosamine-l-phosphate (18), UDP-lV-acetyl-a-D-galactosamine (19), E IV-acetyl-galactosamine kinase (EC 2.7.1. ), F UDP-GalNAc pyrophosphorylase (EC 2.7.7. )...

A de novo synthesis of GDP-Fuc (13), UDP-Gal (16) and UDP-GalNAc (19) by isolated enzymes of the salvage pathways (see Fig. 14) has not yet been described. A crude extract from porcine submaxillary glands gave a yield of 80% for the synthesis of p-L-fucose-1-phosphate (12), but the synthesis of 13 was less successful with a yield of 20% [312]. The main pathways for 16 and 19 involve 4-epimerases (Table 4 and Fig. 14) which are not suitable for preparative synthesis due to their unfavourable equilibrium constants [347, 348], An alternative is Gal-l-P uridyltransferase which is only specific for Gal-l-P and GalNH2-l-P (Table 4). 

Figure 2 Examples of glycosyl donors. Nucleotide donors are represented by UDP-galactose (UDP-Gal), GDP-fucose (GDP-Fuc), GMP-N-acetyIneuraminic acid (CMP-sialic acid, CMP-Neu5Ac), GDP-galactose (GDP-Gal), dTDP-rhamnose (dTDP-Rha), and dTDP-daunosamine lipid phosphate donors are represented by Lipid II and dolichol-phosphate-glucose (Dol-P-GIc) sugar phosphate donors are represented by glucose-1-phosphate. The saccharides are transferred from these donors by GTs to form oligo/polysaccharides and glycoconjugate products.

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