Synthesis and Biological Applications of Glycoconjugates

Indexed in: Chemical Abstracts and Scopus

The interactions between carbohydrates and proteins have been extensively explored in a wide range of physiological and pathological processes over several decades. The recent emergence of glycomics ...
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Monovalent and Multivalent Inhibitors of Bacterial Toxins

Pp. 78-91 (14)

Edward D. Hayes and W. Bruce Turnbull

Abstract

Cholera and travellers' diarrhoea are caused by AB5 protein toxins that bind to ganglioside GM1 at the surface of the cells lining the intestine. Inhibition of this protein-carbohydrate interaction would prevent the toxin from entering the cells, and thus prevents toxin-induced diarrhoea. In this review we will describe the structures of the cholera and E. coli heat-labile toxins, and summarize the main strategies that have led to the development of monovalent and multivalent inhibitors of these toxins. A number of key design concepts emerge from these studies including the importance of pre-organization of the sugar residues within the monovalent ligands, and also the pre-organization of monovalent ligand groups within larger multivalent ligands. The importance of chelation and protein aggregation as mechanisms of multivalent inhibition is also discussed.

Keywords:

bacterial toxin, multivalency, dendrimer, cholera, inhibitor

Affiliation:

School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.