Hemagglutination inhibitors

Sialic acid was the first virus receptor identified. Hirst and McClelland and Hare discovered that influenza virus is able to hemagglutinate and that adsorbed virus is eluted from erythrocytes on incubation at 37°C, indicating an enzymatic destruction of a receptor substance on the cells [1, 2]. When a similar enzymatic activity was subsequently detected in Vibrio cholerae cultures, the term receptor-destroying enzyme was introduced [3]. The substance released by the viral enzyme from soluble hemagglutination inhibitors was initially characterized as a carbohydrate of low molecular weight [4] and then identified in crystalline form as A-acetyl-o-neuraminic acid [5]. Thus, it was clear that the receptor determinant of influenza virus was sialic acid and that the viral enzyme was a neuraminidase. Furthermore, for the first time an important biological function of sialic acid had been identified. 

Finally, the clusters were tested as inhibitors of hemagglutination of pig and rabbit erythrocytes by type-1 piliated UTI89 clinical isolate E. coli. The inhibition titer (IT), that is, the lowest concentration of the inhibitor at which no agglutination occurs, showed tetramer 51 to be the best inhibitor of hemagglutination, with an IT of about 3 fiM, or a factor of 6000 as compared to its affinity, and corresponding to 1000-fold better inhibition than that induced by D-mannose. Overall, tetravalent cluster 51 was the best noncovalent cross-linker of Con A and the best ligand known to E. coli K12 FimH. 

M. Mammen, G. Dahmann, and G. M. Whitesides, Effective inhibitors of hemagglutination by Influenza Virus synthesized from polymers having active ester groups. Insight into mechanisms of inhibition, /. Med. Chem., 38 (1995) 4179-4190. 

L5. Laurell, A.-B., Inhibitor capacity of some purified human serum proteins on hemagglutination by influenza virus. Acta Pathol, et Microbiol. Scand. 49, 213 (1960). 

This cooperative effect of several ligands at the surface of a liposome was recently demonstrated by the inhibition of agglutination of erythrocytes (natural vesicles covered with sialic acids) with the influenza virus by means of sialyl gangliosides. The lowest concentration of sialyl derivatives required for the inhibition was found to be 10 pM in solution whereas it was 20 nM at the surface of a vesicle. Actually, arrays of sialic acid at the surface of liposomes were found to be moderately more effective than sialic acid groups linked to a soluble polymer but as good or better than the best known naturd inhibitors of hemagglutination (i.e. mucins and macroglobulins) [150]. 

Gouin et al. described a heptavalent a-Man-based glycocluster (Fig. 16.9a) as a strong inhibitor to block the hemagglutination of type 1 fimbrial adhesins of E. coli... 

Complex, blood-group-active substances have been employed as inhibitors of hemagglutination.196,693 Osawa and Matsumoto found692 inhibition of both Ulex lectins by human A-, B-, and H-active substances, whereas Lea substance and porcine, submaxillary mucin bound only to Ulex II. Chuba and coworkers693 reported that substances from porcine stomach (A-active), equine stomach (B-active), and baboon stomach (A-, B-, and O-active substances), as well as human A-, B-, and O-active substances, bound equally well to both U. europeus lectins. However, porcine, submaxillary mucin and nonsecretor saliva inhibited only Ulex II activity. 

Extracts from the seeds of Laburnum alpinum were first shown to possess anti-H(O) activity by Renkonen,6 and this was confirmed by Morgan and Watkins22 and others.77,471 Although the L. alpinum lec-tin(s) has not been purified, hemagglutination-inhibition studies conducted on seed extracts reveal a specificity towards N,N -diacetylchitobiosyl residues.19,196,471 Human A, H, and neuraminidase-treated human Lea blood-group substances were also extremely good inhibitors of the Laburnum lectin.198,471... 

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