Synthesis and screening of a library of Lewisx deoxyfluoro-analogues reveals differential recognition by glycan-binding partners
Kristian Hollingsworth,
Antonio Maio,
Sarah-Jane Richards,
Jean-Baptiste Vendeville,
David E. Wheatley,
Claire E. Council,
Tessa Keenan,
Hélène Ledru,
Harriet Chidwick,
Kun Huang,
Fabio Parmeggiani,
Andrea Marchesi,
Wengang Chai,
Ryan McBerney,
Tomasz P. Kamiński,
Matthew R. Balmforth,
Alexandra Tamasanu,
James D. Finnigan,
Carl Young,
Stuart L. Warriner,
Michael E. Webb,
Martin A. Fascione,
Sabine Flitsch,
M. Carmen Galan,
Ten Feizi (),
Matthew I. Gibson (),
Yan Liu (),
W. Bruce Turnbull () and
Bruno Linclau ()
Additional contact information
Kristian Hollingsworth: University of Leeds
Antonio Maio: Imperial College London
Sarah-Jane Richards: University of Warwick
Jean-Baptiste Vendeville: University of Southampton, Highfield
David E. Wheatley: University of Southampton, Highfield
Claire E. Council: University of Southampton, Highfield
Tessa Keenan: University of York
Hélène Ledru: University of Bristol
Harriet Chidwick: University of York
Kun Huang: University of Manchester
Fabio Parmeggiani: University of Manchester
Andrea Marchesi: University of Manchester
Wengang Chai: Imperial College London
Ryan McBerney: University of Leeds
Tomasz P. Kamiński: University of Leeds
Matthew R. Balmforth: University of Leeds
Alexandra Tamasanu: University of Leeds
James D. Finnigan: Prozomix Limited
Carl Young: Prozomix Limited
Stuart L. Warriner: University of Leeds
Michael E. Webb: University of Leeds
Martin A. Fascione: University of York
Sabine Flitsch: University of Manchester
M. Carmen Galan: University of Bristol
Ten Feizi: Imperial College London
Matthew I. Gibson: University of Warwick
Yan Liu: Imperial College London
W. Bruce Turnbull: University of Leeds
Bruno Linclau: University of Southampton, Highfield
Nature Communications, 2024, vol. 15, issue 1, 1-14
Abstract:
Abstract Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues (‘glycofluoroforms’) using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow.
Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51081-7
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DOI: 10.1038/s41467-024-51081-7
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