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Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands

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Richards, Sarah-Jane, Keenan, Tessa, Vendeville, Jean-Baptiste, Wheatley, David E., Chidwick, Harriet, Budhadev, Darshita, Council, Claire E., Webster, Claire S., Ledru, Helene, Baker, Alexander, Walker, Marc, Galan, M. Carmen, Linclau, Bruno, Fascione, Martin A. and Gibson, Matthew I. (2021) Introducing affinity and selectivity into galectin-targeting nanoparticles with fluorinated glycan ligands. Chemical Science . doi:10.1039/D0SC05360K (In Press)

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Official URL: http://dx.doi.org/10.1039/D0SC05360K

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Abstract

Galectins are potential biomarkers and therapeutic targets. However, galectins display broad affinity towards β-galactosides meaning glycan-based (nano)biosensors lack the required selectivity and affinity. Using a polymer-stabilized nanoparticle biosensing platform, we herein demonstrate that the specificity of immobilised lacto-N-biose towards galectins can be ‘turned on/off’ by using site-specific glycan fluorination and in some cases reversal of specificity can be achieved. The panel of fluoro-glycans were obtained by a chemoenzymatic approach, exploiting BiGalK and BiGalHexNAcP enzymes from Bifidobacterium infantis which are shown to tolerate fluorinated glycans, introducing structural diversity which would be very laborious by chemical methods alone. These results demonstrate that integrating non-natural, fluorinated glycans into nanomaterials can encode unprecedented selectivity with potential applications in biosensing.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Q Science > QP Physiology
Divisions: Faculty of Science > Chemistry
Faculty of Science > Physics
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Lectins , Galactose, Ligands (Biochemistry), Glycosylation
Journal or Publication Title: Chemical Science
Publisher: Royal Society of Chemistry
ISSN: 2041-6520
Official Date: 2021
Dates:
DateEvent
2021Published
16 November 2020Available
14 November 2020Accepted
Date of first compliant deposit: 25 November 2020
DOI: 10.1039/D0SC05360K
Status: Peer Reviewed
Publication Status: In Press
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDInnovate UKhttp://dx.doi.org/10.13039/501100006041
EP/K039466/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
BB/M02878X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M028976/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M02847X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M028941/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M01116X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
studentship Iceni Diagnostics Ltd.https://www.icenidiagnostics.com/
EP/K039660/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
EP/M028127/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
EP/S013741/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266

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