Sialyl lactose

H. Oka, T. Onaga, T. Koyama, C.-T. Guo, Y. Suzuki, Y. Esumi, K. Hatano, D. Temnuma, and K. Matsuoka, Sialyl 7(2 3) lactose clusters using carbosilane dendrimer core scaffolds as influenza hemagglutinin blockers, Bioorg. Med. Chem. Lett., 18 (2008) 4405 1408. 

Calciflations were performed using the crystallographic structure of the sialyl lactose-sialoadhesin complex, PDB crystal structure entry IQFO [64]. 

Fig. 7 Comparison of experimental and predicted STD values from CORCEMA-ST protocol for the crystal structure of sialoadhesin-sialyl lactose complex at protein/ligand ratio of 1 300. Reprinted from [63] 2004, with permission from Elsevier...

Figure 2.19 Sialylation ofN-acetyl lactose by cytidyl monophosphate-N-acetylneuraminic acid using Of 2,3-neuraminic acid transferase as catalyst (upper box). Regeneration of the sugar nucleotide is shown in the lower box. CMP is converted into CTP in two steps using two different kinases. In the final step CMP-A -acetylneuraminic acid is synthesised from CTP and A -acetylneuraminic acid (sialic acid) using the appropriate synthetase. The formed pyrophosphate is converted into inorganic phosphate. Altogether five different enzymes are involved in the process.

In the initial studies, as briefly described earlier, the methyl a-2-thioglycoside of Neu5Ac 5 [22,24], or the -1 1 anomeric mixture 11 [26,27], which can be almost quantitatively prepared from 9 in one step, was coupled with lightly protected sugar acceptors such as 14,16, and 18 in the presence of DMTST in acetonitrile to give exclusively the sialyl a(2—>3)- or sialyl ot(2—>6)-D-galactose or lactose derivatives (20, 22, and 24) in 50-70% yields even in large-scale reactions [26],... 

The 3-OH group of lactose or IV-acetyl-lactosamine is the site of glycosylation in some biologically important glycoprotein and glycolipids.75 For instance, L-fucose is linked to 0-3 of IV-acetyl-lactosamine in the Lewisx trisaccharide determinant (25), and sialic acid is linked to 0-3 of the galactose residue in sialyl... 

Besides the common organic solvents used for glycosylations, syntheses of glycosides from glycosyl phosphites in ionic liquids were recently reported [463]. Glycosyl phosphites are frequently used for sialylations [451,454] and a typical example is shown in Scheme 4.44. As illustrated, reaction of the (3-neuraminyl phosphite 205 with the lactose diol 206 afforded the 3-(9-neuraminyllactose derivative 207 in a 55% yield [460]. 

Modifications at positions 4 (not shown in Table 16.3), 8 (entry 6) and 9 (entry 7) of the terminal sialic acid are detrimental to activity, whereas deoxygenation at C-7 (entry 5) slightly improves the activity compared with a(2-3)-sialyl lactose (entry 1). Interestingly, the replacement of the entire terminal NeuSAc moiety by Kdn (2-keto-3-deoxy-D-glycero-D-gfl(acfo-nononic acid entry 8) resulted in a 6.5-fold improved inhibition compared with the NeuSAc-containing analog (entry 13). 

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