Helicobacter pylori, a Gram-negative bacterium found in the stomach, is a major cause of gastritis, peptic ulcers and stomach cancer.[1] 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.[2] By varying the pH of the environment of BabA, it was possible to change its binding preferences towards Lewis b structures.[3] 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.[4] Upon global deprotection by Pd-catalysed hydrogenolysis, isothiocyanate methodology was employed to facilitate conjugation of the glycan to Bovine Serum Albumin (BSA).
Figure 1 – Lewis b structures attached to an amino-propyl hydrochloride spacer.
- Graham, D. Y. Gastroenterology 1989, 96, 615–625.
- Sweeney, E. G.; Guillemin, K. Cell Host Microbe 2016, 19, 5–7.
- Bugaytsova, J. A. et al. Cell Host Microbe 2017, 21, 376–38.
- Lemieux, R. U. et al. J. Am. Chem. Soc. 1975, 97, 4056–4062.
