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Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli

Natalie Hanheiser, Badri Parshad, Tatyana L. Povolotsky, Vinod Khatri, Katharina Achazi, Sumati Bhatia Orcid Logo

Macromolecular Chemistry and Physics

Swansea University Author: Sumati Bhatia Orcid Logo

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DOI (Published version): 10.1002/macp.202300339

Abstract

Here, we demonstrate the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides [LPG40Man0.60 and LPG40(Manα1,2Man)0.60]. A method based on label-free microscale thermophoresis (MST) has been optimized to determine the direct binding affinity of multivalent mannosides for...

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Published in: Macromolecular Chemistry and Physics
ISSN: 1022-1352 1521-3935
Published: Wiley 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa64850
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Abstract: Here, we demonstrate the synthesis of linear polyglycerols bearing multiple copies of mono and dimannosides [LPG40Man0.60 and LPG40(Manα1,2Man)0.60]. A method based on label-free microscale thermophoresis (MST) has been optimized to determine the direct binding affinity of multivalent mannosides for Escherichia coli (E. coli) strain ORN178 that produces the fimbriae protein FimH. We observed that the LPG40(Manα1,2Man)0.60 exhibited only a modest one-fold improvement in binding as compared to LPG40Man0.60. Nevertheless, both the multivalent mannosides displayed remarkably very low nM binding constant (Kd) in contrast to the high μM Kd of the single α-D-methylmannoside for intact E. coli ORN 178 particles. Furthermore, in an Adhesion-Inhibition Assay, both multivalent mannosides showed 50% inhibition of bacteria adhesion to the HT-29 colon cells at low μM concentrations.
Keywords: Adhesion inhibition, Escherichia coli, glycopolymers, microscale thermophoresis, poly(Manα1,2Man), polyMan
College: Faculty of Science and Engineering
Funders: This work is supported by funding from the Deutsche Forschungsgemeinschaft (DFG) – Projektnummer 458564133. Open access funding enabled and organized by Projekt DEAL.