Article

A simple and accessible synthetic lectin for glucose recognition and sensing

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Abstract

Binding carbohydrates from water is a difficult task, even for the natural carbohydrate-binding proteins known as lectins. The design of synthetic lectin mimics is correspondingly challenging, especially if good selectivities are required. In previous work we showed that success is possible, but only for complex polycyclic architectures that require lengthy and low-yielding syntheses; for example, one glucose-selective system was made in 21 steps and only 0.1% overall yield. Here we report the discovery of a simple monocyclic host that matches the earlier designs, but is far more accessible as it is prepared in just five steps and 23% overall yield. The new synthetic lectin binds glucose with excellent selectivity versus other common monosaccharides (for example, 50:1 versus galactose) and sufficient affinity for glucose sensing at the concentrations found in blood. It also features a built-in signalling system in the form of strong and guest-dependent fluorescence emission. The effectiveness and simplicity of this molecule suggests the potential for development into a new methodology for practical glucose monitoring.

  • Compound C6H12O6

    β-D-Glucose

  • Compound C132H148N12O5212-

    Bis-dipropoxybiphenyl tetra-isophthalamido tricyclic synthetic lectin dodecacarboxylate

  • Compound C16H16N2

    Anthracene-9,10-diyldimethanamine

  • Compound C46H49F10NO14

    Bis(perfluorophenyl) 5-((9-((3-(tert-butoxy)-3-oxopropoxy)methyl)-2,2,16,16-tetramethyl-4,14-dioxo-3,7,11,15-tetraoxaheptadecan-9-yl)carbamoyl)isophthalate

  • Compound C76H72N6O246-

    Bis-anthracenyl di-isophthalamido monocyclic synthetic lectin hexacarboxylate

  • Compound C22H6F10O6

    1-Methyl 3,5-bis(perfluorophenyl) benzene-1,3,5-tricarboxylate

  • Compound C25H47NO9

    Di-tert-butyl 3,3'-((2-amino-2-((3-(tert-butoxy)-3-oxopropoxy)methyl)propane-1,3-diyl)bis(oxy))dipropanoate

  • Compound C41H52F5NO14

    1-Methyl 3-(perfluorophenyl) 5-((9-((3-(tert-butoxy)-3-oxopropoxy)methyl)-2,2,16,16-tetramethyl-4,14-dioxo-3,7,11,15-tetraoxaheptadecan-9-yl)carbamoyl)isophthalate

  • Compound C68H68N6O246-

    Anthracenyl phenyl di-isophthalamido monocyclic synthetic lectin hexacarboxylate

  • Compound C7H14O6

    Methyl β-D-glucoside

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Acknowledgements

The authors dedicate this manuscript to J. F. Stoddart on the occasion of his 70th birthday. This research was supported by the Royal Society (Newton International Fellowship to C.K.) and the EPSRC (Institutional Sponsorship 2011). NMR equipment was funded in part by the Wellcome Trust (WT082352).

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Affiliations

  1. School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK

    • Chenfeng Ke
    • , Harry Destecroix
    • , Matthew P. Crump
    •  & Anthony P. Davis

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Contributions

The experimental work was performed mainly by C.K., with a contribution from H.D. towards the synthesis of 9. C.K., A.P.D. and M.P.C. planned the work and analysed the results. The paper was co-written by C.K. and A.P.D., with assistance from the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Anthony P. Davis.

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