Sialic acid-binding toxins

Heerze, L D, Smith, R H, Wang, N, Armstrong, G D, Utilization of sialic acid-binding synthetic peptide sequences derived from pertussis toxin as novel anti-inflammatory agents, Glycobiology, 5, 427-433, 1995. 

Baker HM, Basu I, Chung MC et al. Crystal structures of the staphylococcal toxin SSL5 in complex with sialyl Lewis X reveal a conserved binding site that shares common features with viral and bacterial sialic acid binding proteins. J Mol Biol 2007 374 1298-1308. 

In both of these cases, the ligand (sialic acid) for the analyte of interest (influenza vims) was covalently linked to the PDA backbone generated upon photopolymerization. Functional sensors based on ligands that are noncovalently incorporated into liposomes have also been reported (Charych et al. 1996 Pan and Charych 1997). Mixed liposomes as well as mixed thin films on glass containing a combination of the ganglioside GMl and diacetylene lipids detect the presence of cholera toxin, a protein that binds to GMl. 

Cholera toxin consists of one 240-residue A subunit and a ring of five 103-residue B subunits.c e The latter is a "targeting complex," a bacterial lectin each subunit of which binds to the galactose and sialic acid termini of a single molecule of ganglioside Gm1. 

Isoda, H., Kawasaki, Y., Tanimoto, M., Dosako, S., and Idota, T. 1990. Use of compounds containing or binding sialic acid to neutralize bacterial toxins. European Patent No. 385112. 

Sialic acids are involved in a number of biological processes including cell-to-cell, cell-to-microorganism, -toxin, and -antibody binding. Their importance in these processes, especially those with relevance to human disease states, has led to interest in the synthesis of both natural and modified sialic acids. This review examines the most recent methods used for the synthesis and modification of sialic acids and for the preparation of sialyl glycosides as biological probes of sialic acid-recognising proteins. 

Based on the functional similarities between the pertussis toxin and the selectins (including their ability to bind to similar sialic acid-containing oligosaccharides structures), Rozdzinski et al. [166] and Heerze et al. [169] synthesized peptides from the regions of sequence similarity in an effort to find molecules that adhere to sialic acid-containing glycoconjugates. The recombinant subunits S2 and S3 of pertussis toxin and the synthetic peptides competitively inhibited adherence of neutrophils to selectin-coated surfaces and to endothelial cells in vitro. 

Pathogenic microorganisms and toxins binding to sialic acids on host cells... 

It should also be mentioned that several bacterial toxins are known which bind to gangliosides in a sialic-acid-dependent manner, e.g. cholera, pertussis and tetanus toxins... 

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