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Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to Epithelial Cells
Author(s) -
Machida Takuya,
Novoa Alexandre,
Gillon Émilie,
Zheng Shuangshuang,
Claudi Julie,
Eierhoff Thorsten,
Imberty Anne,
Römer Winfried,
Winssinger Nicolas
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201700813
Subject(s) - glycan , fucose , lectin , chemistry , nucleic acid , biochemistry , cooperativity , cell adhesion , microbiology and biotechnology , glycoprotein , cell , biology
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.