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

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

doi:10.1002/macp.202300339

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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

Macromolecular Chemistry and Physics

Swansea University Author: Sumati Bhatia

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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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spelling	v2 64850 2023-11-01 Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM 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. Journal Article Macromolecular Chemistry and Physics Wiley 1022-1352 1521-3935 Adhesion inhibition, Escherichia coli, glycopolymers, microscale thermophoresis, poly(Manα1,2Man), polyMan 8 11 2023 2023-11-08 10.1002/macp.202300339 http://dx.doi.org/10.1002/macp.202300339 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University Other This work is supported by funding from the Deutsche Forschungsgemeinschaft (DFG) – Projektnummer 458564133. Open access funding enabled and organized by Projekt DEAL. 2023-12-04T12:27:33.7293266 2023-11-01T10:30:57.5141397 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Natalie Hanheiser 1 Badri Parshad 2 Tatyana L. Povolotsky 3 Vinod Khatri 4 Katharina Achazi 5 Sumati Bhatia 0000-0002-5123-4937 6 64850__29180__7de382ea1783410fb01dbe2273bb041f.pdf 64850.VOR.pdf 2023-12-04T12:23:54.1895175 Output 661138 application/pdf Version of Record true © 2023 The Authors. Macromolecular Chemistry and Physics published by Wiley-VCH GmbH. Distributed under the terms of a Creative Commons Attribution 4.0 International License (CC BY 4.0). true eng https://creativecommons.org/licenses/by/4.0/
title	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
spellingShingle	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli Sumati Bhatia
title_short	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
title_full	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
title_fullStr	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
title_full_unstemmed	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
title_sort	Synthesis and Comparison of Linear Polymannosides for Direct Binding with Escherichia Coli
author_id_str_mv	a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv	a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author	Sumati Bhatia
author2	Natalie Hanheiser Badri Parshad Tatyana L. Povolotsky Vinod Khatri Katharina Achazi Sumati Bhatia
format	Journal article
container_title	Macromolecular Chemistry and Physics
publishDate	2023
institution	Swansea University
issn	1022-1352 1521-3935
doi_str_mv	10.1002/macp.202300339
publisher	Wiley
college_str	Faculty of Science and Engineering
hierarchytype
hierarchy_top_id	facultyofscienceandengineering
hierarchy_top_title	Faculty of Science and Engineering
hierarchy_parent_id	facultyofscienceandengineering
hierarchy_parent_title	Faculty of Science and Engineering
department_str	School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
url	http://dx.doi.org/10.1002/macp.202300339
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description	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.
published_date	2023-11-08T12:27:34Z
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score	11.013731

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

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