Agglutination inhibitors

Mortell KH, Gingras M, Kiessling LL (1994) Synthesis of cell agglutination inhibitors by aqueous ring-opening metathesis polymerization. J Am Chem Soc 116(26) 12053-12054... 

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. 

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]. 

For enzyme inhibition assays, urine is the preferred specimen [4]. Interestingly, Bik can be measured by the inhibition of trypsin in urine but not in plasma. Urinary Bik analysis may also be performed by antibody staining, latex agglutination, and radioimmunoassay (RIA) [4]. Despite the analytical approach used, all Bik forms are measured together. The enzyme inhibition method involves adding known amounts of trypsin to the specimen and monitoring trypsin inhibition. Trypsin activity is assessed by detection of by-products from a cleavable substrate. Dipstick methods are available for the rapid detection of trypsin inhibitors in urine [15, 17 19]. 

Lima-bean lectin precipitated blood-group A and B secretor saliva, but not O it did not precipitate the saliva of any nonsecretors.2,3,103 Kriipe77 substantiated Boyd s results, using secretor saliva as an inhibitor of lima-bean lectin-erythrocyte agglutination. Types A,B, A,A2, AiO, and A20 saliva all inhibited the lima-bean lectin, whereas type OO saliva and type OO ovarian-cyst material were noninhibitory. 

Some of the proteins are toxic in nature. Ricin present in castor bean is extremely toxic to higher animals in very small amounts. Enzyme irvhibitors such as trypsin inhibitor bind to digestive enzyme and prevent the availability of the protein. Lectin, a toxic protein present commonly in legumes, agglutinates red blood cells. A bacterial toxin causes cholera, which is a protein. Snake venom is protein in nature. 

To dissect the contributions of classical multivalent effects from the steric mechanism. White-sides and coworkers demonstrated that when monomeric sialic acid derivatives were added along with the acrylamide polymer, more efficient (on a molar sialic acid basis) inhibition of agglutination was observed [149,162,163]. Addition of the monomeric inhibitors is proposed to have two effects. First, displacement of a polymer-displayed ligand by monomer would lower the affinity of the polymer for the surface of the virus. Second, the size of the polymer not bound to the surface is necessarily increased, and thereby increases the ability of the polymer... 

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