1. Synthesis and screening of a library of Lewis x deoxyfluoro-analogues reveals differential recognition by glycan-binding partners.
- Author
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Hollingsworth K, Di Maio A, Richards SJ, Vendeville JB, Wheatley DE, Council CE, Keenan T, Ledru H, Chidwick H, Huang K, Parmeggiani F, Marchesi A, Chai W, McBerney R, Kamiński TP, Balmforth MR, Tamasanu A, Finnigan JD, Young C, Warriner SL, Webb ME, Fascione MA, Flitsch S, Galan MC, Feizi T, Gibson MI, Liu Y, Turnbull WB, and Linclau B
- Subjects
- Protein Binding, Binding Sites, Humans, Halogenation, Lewis X Antigen metabolism, Lewis X Antigen chemistry, Nanoparticles chemistry, Polysaccharides metabolism, Polysaccharides chemistry
- 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 Lewis
x 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., (© 2024. The Author(s).)- Published
- 2024
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