Bifunctional Linkers for the Generation of Multivalent Neoglycoproteins

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Programme Social programme Plenary speakers Keynote speakers 1st EuroCarb Young Researcher (ECYR) Workshop CarboMet Workshop Mini symposium: Glycobiology at the LUMC and beyond Favourites/Agenda

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1st EuroCarb Young Researcher (ECYR) Workshop

CarboMet Workshop

Mini symposium: Glycobiology at the LUMC and beyond

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Bifunctional Linkers for the Generation of Multivalent Neoglycoproteins

Ryan Mcberney 1 , Michael E. Webb 1 , W. Bruce Turnbull 1

1 University Of Leeds, Leeds , United Kingdom

Bacterial toxins have efficiently evolved to effectively gain entry into host organisms. Infection often leads to diarrhoeal disease, dehydration and potential death.1 The AB5 family of toxins, contain a pentameric B-subunit binding lectin which binds cell surface glycolipids.2 Binding multiple copies of the glycolipid gives rise to very high affinity interactions, which aids the cellular uptake of the toxin.3 Inhibiting these interactions would lead to prevention of toxin entry and disease. Site specific modification of the cholera toxin B-subunit has shown to present carbohydrates with optimal geometry and valency for toxin binding, and an attractive method of creating complex multivalent inhibitors.4 Here, we present the use of novel bi-functional, bio-orthogonal linkers for the functionalisation of oligosaccharides for the glycosylation of mutant bacterial B subunits. The novel linker can be used neoglycoproteins bearing different oligosaccharides on different faces of the proteins, for the generation of bacterial toxin inhibitors against various toxins.

Multiple site functionalisation of a protein scaffold, with chemically reactive globotrioside (Gb3) and GM1 pentasaccharide using a single Bicyclononyne (BCN) linker.

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W. B. Turnbull, B. L. Precious and S. W. Homans, J. Am. Chem. Soc., 2004, 126, 1047–1054.

T. E. McAllister, M. A. Fascione, T. R. Branson, W. B. Turnbull, J. Garcia-Hartjes, T. Wennekes, J. F. Ross, H. Zuilhof and S. L. Warriner, Angew. Chemie Int. Ed., 2014, 53, 8323–8327.

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