Synthesis of b-Lewis b to investigate binding preferences of helicobacter pylori

Session: 
S10.2 Cell surface glycans
Code: 
OL10.2.2
Location (hall): 
Mannose
Start/end time: 
Thursday, July 4, 2019 - 17:30 to 17:45
Mark
Reihill

Mark Reihill1, Aisling Ní Cheallaigh1, Stefan Oscarson1

1School of Chemistry, University College Dublin, Dublin, Ireland

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.

References: 
  1. Graham, D. Y. Gastroenterology 1989, 96, 615–625.
  2. Sweeney, E. G.; Guillemin, K. Cell Host Microbe 2016, 19, 5–7.
  3. Bugaytsova, J. A. et al. Cell Host Microbe 2017, 21, 376–38.
  4. Lemieux, R. U. et al. J. Am. Chem. Soc. 1975, 97, 4056–4062.

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