Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to Epithelial Cells

Angewandte Chemie
Takuya MachidaNicolas Winssinger

Abstract

Pathogens frequently rely on lectins for adhesion and cellular entry into the host. Since these interactions typically result from multimeric binding of lectins to cell-surface glycans, novel therapeutic strategies are being developed with the use of glycomimetics as competitors of such interactions. Herein we study the benefit of nucleic acid based oligomeric assemblies with PNA-fucose conjugates. We demonstrate that the interactions of a lectin with epithelial cells can be inhibited with conjugates that do not form stable assemblies in solution but benefit from cooperativity between ligand-protein interactions and PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully blocked the binding of the fucose-binding lectin BambL of Burkholderia ambifaria, a pathogenic bacterium, to epithelial cells with an efficiency of more than 700-fold compared to l-fucose.

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Citations

Jul 15, 2018·Chemistry : a European Journal·Hyeongjoo Choi, Yongwon Jung
Sep 2, 2020·Chemical Society Reviews·Sean B Yeldell, Oliver Seitz
Dec 6, 2017·Chemistry : a European Journal·Nicolas ProbstSamir Messaoudi
Feb 12, 2020·Carbohydrate Research·Thomas Bachmann, Michael Rychlik
Apr 24, 2021·Chembiochem : a European Journal of Chemical Biology·Yiran Huang, Xiaoyu Li
Jun 16, 2021·Bioorganic & Medicinal Chemistry·Phuong Luong, Danielle H Dube
Feb 3, 2018·Journal of the American Chemical Society·Zutao YuHiroshi Sugiyama
Mar 15, 2019·Bioconjugate Chemistry·Kiefer O RambergPeter B Crowley
Jun 17, 2020·Journal of the American Chemical Society·Simona Angerani, Nicolas Winssinger
Mar 4, 2020·ACS Sensors·Dalu ChangNicolas Winssinger
Nov 10, 2018·Journal of the American Chemical Society·Yu ZhouXiaoyu Li

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