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

Angewandte Chemie - International Edition

5 years ago

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

Takuya Machida, Julie Claudinon, Thorsten Eierhoff, Anne Imberty, Winfried Römer, Alexandre Novoa, Émilie Gillon, Shuangshuang Zheng, Nicolas Winssinger

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. Short and sweet: The interactions of lectins (blue) with cells can be inhibited with nucleic acid based oligomeric assemblies with PNA–fucose conjugates. These conjugates do not form stable assemblies in solution but benefit from cooperativity between ligand–protein interactions and PNA hybridization. A dynamic dimeric assembly fully blocked the binding of the fucose-binding lectin BambL of the pathogenic bacterium Burkholderia ambifaria to epithelial cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201700813