| Title: |
Synthesis and screening of a library of Lewis x deoxyfluoro-analogues reveals differential recognition by glycan-binding partners |
| Authors: |
Hollingsworth, Kristian; Di Maio, Antonio; Richards, Sarah Jane; Vendeville, Jean Baptiste; Wheatley, David E.; Council, Claire E.; Keenan, Tessa; Ledru, Hélène; Chidwick, Harriet; Huang, Kun; Parmeggiani, Fabio; Marchesi, Andrea; Chai, Wengang; McBerney, Ryan; Kamiński, Tomasz P.; Balmforth, Matthew R.; Tamasanu, Alexandra; Finnigan, James D.; Young, Carl; Warriner, Stuart L.; Webb, Michael E.; Fascione, Martin A.; Flitsch, Sabine; Galan, M. Carmen; Feizi, Ten; Gibson, Matthew I.; Liu, Yan; Turnbull, W. Bruce; Linclau, Bruno |
| Publication Year: |
2024 |
| Collection: |
University of Southampton: e-Prints Soton |
| Description: |
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 Lewis x . Notably, we show that for two proteins with unique binding sites for Lewis x , 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.soton.ac.uk/495213/1/s41467-024-51081-7.pdf; Hollingsworth, Kristian, Di Maio, Antonio and Richards, Sarah Jane , et al. (2024) Synthesis and screening of a library of Lewisx deoxyfluoro-analogues reveals differential recognition by glycan-binding partners. Nature Communications, 15 (1), [7925]. (doi:10.1038/s41467-024-51081-7 ). |
| Availability: |
https://eprints.soton.ac.uk/495213/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.E9F6F18A |
| Database: |
BASE |