Helicobacter pylori, a Gram-negative bacterium found in the stomach, is a major cause of gastritis, peptic ulcers and stomach cancer. The bacterium uses a membrane-bound lectin, Blood-group Antigen Binding Adhesin (BabA), to bind to Lewis b structures displayed on the surfaces of host cells. By varying the pH of the environment of BabA, it was possible to change its binding preferences towards Lewis b structures. Multivalent presentations of the Lewis b hexasaccharide, along with A- and B-Lewis b, will allow variable pH studies to be performed and determine how the binding preferences of BabA change.
A linear synthesis of B-Lewis b will be presented. Preparation of the heptasaccharide commenced with a 3’-OH lactoside acceptor, obtained via reductive ring-opening of a 3’,4’-endo-O-benzylidene acetal. NIS/AgOTf-promoted glycosylations yielded the desired 1,2-trans linkages while Lemieux’s halide-assisted glycosylation conditions were used to install the 1,2-cis linkages. Upon global deprotection by Pd-catalysed hydrogenolysis, isothiocyanate methodology was employed to facilitate conjugation of the glycan to Bovine Serum Albumin (BSA).
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