Synthesis of fucose derivatives with thiol motifs towards suicide inhibition of helicobacter pylori
| Autor: | Han Remaut, Lorenzo Guazzelli, Mark Reihill, Stefan Oscarson |
|---|---|
| Přispěvatelé: | Department of Bio-engineering Sciences, Structural Biology Brussels |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lewis b
Disulfide Linkage Pharmaceutical Science H. pylori 01 natural sciences Fucose Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry Thiols ABO blood group system Lectins Drug Discovery Suicide inhibitors antivirulence Physical and Theoretical Chemistry chemistry.chemical_classification helicobacter biology 010405 organic chemistry Organic Chemistry Lectin Biological activity fucose derivatives 0104 chemical sciences BabA Bacterial adhesin adhesion chemistry Biochemistry Chemistry (miscellaneous) Suicide inhibition Thiol biology.protein Molecular Medicine 030211 gastroenterology & hepatology |
| Zdroj: | Molecules Volume 25 Issue 18 Molecules, Vol 25, Iss 4281, p 4281 (2020) |
| Popis: | The syntheses of six thiol-exhibiting monosaccharides towards suicide inhibition of Helicobacter pylori are reported. Blood group Antigen Binding Adhesin (BabA), a bacterial membrane-bound lectin, binds to human ABO and Lewis b blood group structures displayed on the surface of host epithelial cells. Crystal structures of the carbohydrate-recognition domain revealed a conserved disulfide bonded loop that anchors a critical fucose residue in these blood group structures. Disruption of this loop by N-acetylcysteine results in reduced BabA-mediated adherence to human gastric tissue sections and attenuated virulence in Lewis b-expressing transgenic mice. With a view of creating specific inhibitors of the lectin, we designed and successfully synthesised six fucose-derived compounds with thiol motifs to engage in a thiol-disulfide exchange with this disulfide bond of BabA and form a glycan-lectin disulfide linkage. Branching and extending the fucose backbone with 2- and 3-carbon thiol motifs delivered a range of candidates to be tested for biological activity against BabA. |
| Databáze: | OpenAIRE |
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