Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers

Abstract Membrane‐active antimicrobial polymers (APs) are promising alternatives for treating infectious diseases as they are less susceptible to antimicrobial resistance development. However, their non‐specific cytotoxicity limits their clinical application. One interesting strategy to improve cyto...

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Main Authors: Alain M. Bapolisi, Steffen Tank, Anne‐Catherine Lehnen, Antje Stindt, Rujuta Athavale, Jan A. M. Kurki, Sany Chea, Sophia Rosencrantz, Ruben R. Rosencrantz, Katja M. Arndt, Matthias Hartlieb
Format: Article
Language:English
Published: Wiley-VCH 2025-08-01
Series:Advanced Materials Interfaces
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Online Access:https://doi.org/10.1002/admi.202500273
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author Alain M. Bapolisi
Steffen Tank
Anne‐Catherine Lehnen
Antje Stindt
Rujuta Athavale
Jan A. M. Kurki
Sany Chea
Sophia Rosencrantz
Ruben R. Rosencrantz
Katja M. Arndt
Matthias Hartlieb
author_facet Alain M. Bapolisi
Steffen Tank
Anne‐Catherine Lehnen
Antje Stindt
Rujuta Athavale
Jan A. M. Kurki
Sany Chea
Sophia Rosencrantz
Ruben R. Rosencrantz
Katja M. Arndt
Matthias Hartlieb
author_sort Alain M. Bapolisi
collection DOAJ
description Abstract Membrane‐active antimicrobial polymers (APs) are promising alternatives for treating infectious diseases as they are less susceptible to antimicrobial resistance development. However, their non‐specific cytotoxicity limits their clinical application. One interesting strategy to improve cytocompatibility is the incorporation of sugar units into APs. This approach takes advantage of specific interactions between sugars and protein receptors, such as lectins, on the surface of bacteria, potentially allowing for discrimination between different bacterial types. However, there is limited research on how sugar addition to cationic APs affects their selectivity and interactions with lectins. Herein, a library of acrylamide‐based cationic glycopolymers is synthesized by a xanthate‐supported photo‐initiated Reversible Additon‐Fragmentation chain Trasnfer (XPI‐RAFT) polymerization. Diverse sugars are added to this cationic scaffold by either chain extension with glycomonomers (based on fucose, glucose, mannose, and polyhydroxy acrylamide) or simply by reductive amination (lactose and melibiose). Various analytical techniques are used to probe the interaction of (glyco)polymers with bacteria, membrane models, and lectins. In general, (glyco)polyhydroxy incorporation proves to reduce the hydrophobicity of the cationic APs and consequently enhances hemocompatibility while maintaining the antimicrobial activity. Although sugar‐protein‐specific recognition may contribute to selectivity, the results demonstrate that electrostatic interaction predominantly drives the binding efficacy of cationic glycopolymers to bacterial membranes.
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spelling doaj-art-675a630234364775b1e248c0e974d6e82025-08-25T08:06:18ZengWiley-VCHAdvanced Materials Interfaces2196-73502025-08-011216n/an/a10.1002/admi.202500273Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic GlycopolymersAlain M. Bapolisi0Steffen Tank1Anne‐Catherine Lehnen2Antje Stindt3Rujuta Athavale4Jan A. M. Kurki5Sany Chea6Sophia Rosencrantz7Ruben R. Rosencrantz8Katja M. Arndt9Matthias Hartlieb10Institute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyMolecular Biotechnology Institute of Biochemistry and Biology University of Potsdam Karl‐Liebknecht Strasse 24–25 14476 Potsdam GermanyInstitute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyInstitute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyInstitute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyInstitute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyFraunhofer Institute for Applied Polymer Research IAP Geiselbergstraße 69 14476 Potsdam GermanyFraunhofer Institute for Applied Polymer Research IAP Geiselbergstraße 69 14476 Potsdam GermanyFraunhofer Institute for Applied Polymer Research IAP Geiselbergstraße 69 14476 Potsdam GermanyMolecular Biotechnology Institute of Biochemistry and Biology University of Potsdam Karl‐Liebknecht Strasse 24–25 14476 Potsdam GermanyInstitute of Chemistry University of Potsdam Karl‐Liebknecht‐Straße 24–25 14476 Potsdam GermanyAbstract Membrane‐active antimicrobial polymers (APs) are promising alternatives for treating infectious diseases as they are less susceptible to antimicrobial resistance development. However, their non‐specific cytotoxicity limits their clinical application. One interesting strategy to improve cytocompatibility is the incorporation of sugar units into APs. This approach takes advantage of specific interactions between sugars and protein receptors, such as lectins, on the surface of bacteria, potentially allowing for discrimination between different bacterial types. However, there is limited research on how sugar addition to cationic APs affects their selectivity and interactions with lectins. Herein, a library of acrylamide‐based cationic glycopolymers is synthesized by a xanthate‐supported photo‐initiated Reversible Additon‐Fragmentation chain Trasnfer (XPI‐RAFT) polymerization. Diverse sugars are added to this cationic scaffold by either chain extension with glycomonomers (based on fucose, glucose, mannose, and polyhydroxy acrylamide) or simply by reductive amination (lactose and melibiose). Various analytical techniques are used to probe the interaction of (glyco)polymers with bacteria, membrane models, and lectins. In general, (glyco)polyhydroxy incorporation proves to reduce the hydrophobicity of the cationic APs and consequently enhances hemocompatibility while maintaining the antimicrobial activity. Although sugar‐protein‐specific recognition may contribute to selectivity, the results demonstrate that electrostatic interaction predominantly drives the binding efficacy of cationic glycopolymers to bacterial membranes.https://doi.org/10.1002/admi.202500273antimicrobial polymersglycopolymerslectin bindingPI‐RAFTRAFT polymerization
spellingShingle Alain M. Bapolisi
Steffen Tank
Anne‐Catherine Lehnen
Antje Stindt
Rujuta Athavale
Jan A. M. Kurki
Sany Chea
Sophia Rosencrantz
Ruben R. Rosencrantz
Katja M. Arndt
Matthias Hartlieb
Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
Advanced Materials Interfaces
antimicrobial polymers
glycopolymers
lectin binding
PI‐RAFT
RAFT polymerization
title Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
title_full Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
title_fullStr Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
title_full_unstemmed Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
title_short Sugars in Antimicrobial Polymers – The Impact of Sugar‐Lectin Binding in Membrane Interaction of Cationic Glycopolymers
title_sort sugars in antimicrobial polymers the impact of sugar lectin binding in membrane interaction of cationic glycopolymers
topic antimicrobial polymers
glycopolymers
lectin binding
PI‐RAFT
RAFT polymerization
url https://doi.org/10.1002/admi.202500273
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