Sialic acids substitution

SLe mimics 46 to 48, which had the GlcNAc unit replaced by (R,/ )-cyclohexan-l,2-diol and sialic acid substituted by glycolic acid or (5)-cyclohexyl lactic acid, were active as antagonists (Figure 16.21). These observations are in agreement with predictions based on computational studies that suggested these compounds are able to adopt the bioactive conformation. These computational simulations further predicted that the (/f)-lactic acid isomers were inactive because of their inability to properly orient the pharmacophores. Indeed, replacement of sialic acid by... 

A. Sialic Acid Substituted Polymers Are Highly Effective Inhibitors... 

Several groups have generated sialic acid substituted acrylamide polymers and investigated the abilities of these materials to inhibit influenza virus HA [101,162, 166,170,174]. In these investigations, the mole fraction of A-acetylneuraminic acid (NeuAc) residues displayed by the different acrylamide polymers has been varied. The potency of the materials generated depends on the degree of substitution on the polymers. Maximal polymer activity was observed when approximately 10-20% of the units were substituted with NeuAc. Lower amounts of substitution resulted in decreased functional affinities, presumably because these materials were less likely... 

Brinkmann-van der Linden ECM, Sonnenburg JL, Varki A (2002) Effects of sialic acid substitutions on recognition by Sambucus nigra agglutinin and Maackia amurensis Hemagglutinin. Anal Biochem 303 98-104... 

Periodate oxidation of sialic acids had earlier been used for structural determination of O-substituted sialic acids.89 Whereas, for example, one mole of a 4-O-acetylated sialic acid consumes 2 moles of periodate within 10-20 min at 0°, the same amount of the 7-O-acetyl isomer is oxidized by only one mole. As already discussed in connection with the periodic acid-thiobarbituric acid assay, 9-O-substituted sialic acids exhibit a very low rate of oxidation as compared with the unsubstituted sialic acids13 this observation originally led to the erroneous assignment89 of the 9-O-acetyl group to 0-8. All other sialic acids having O-acetyl groups on the side chain are expected to be unaffected by periodate. 

In view of the appearance ol neuraminic acid in evolution, the question must be posed as to which molecule pre-existed, and may still be found, in those primitive animals unable to synthesize sialic acids where comparable functions might be expected, for example, in cell membranes, or in the nervous system. Are such molecules uronic acids, or neutral sugars, substituted by such acids as phosphoric or sulfuric acid At this point, the present essay may he concluded by point-... 

In glycoproteins, L-fucose and sialic acid are often mutually exclusive at some sites of substitution, and both sugars occur at nonreducing termini.118 In fact, they have been assumed to act as chain-stoppers" in the biosynthetic process, controlling the extent of chain elongation. Nevertheless, from the jelly coat of the eggs of the sea ur-... 

The sialic acid aldolase-catalyzed condensation of D-mannose 8 and pyruvate led, in an excellent yield, to the synthesis of KDN 9 [33], a natural deaminated neuraminic acid first isolated from rainbow trout eggs [34] and then discovered in other species. The discovery that sialic acid aldolase accepts as substrates D-mannose substituted on the 2-position, even by bulky substituents such as phenyl, azido, or bromine, opened the route to novel unnatural sialic acid derivatives [35-39]. Pentoses also are substrates. N-Substituted neuraminic acids could be prepared either directly from the corresponding Af-substituted mannosamine, such as N-thioacyl derivatives [40], or after reduction and acylation of 5-azido-KDN [41]. Recently, AT-carbobenzyloxy-D-mannosamine was converted, in a good yield, into the N-carbobenzyloxy-neurarninic acid, further used as a precursor of a derivative of castanospermine [42]. 

A. Buensch, J. C. Paulson, and R. Brossmer, Activation and transfer of novel synthetic 9-substituted sialic acids, Eur. J. Biochem. 168 595 (1987). 

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