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A biomimetic receptor for glucose


Specific molecular recognition is routine for biology, but has proved difficult to achieve in synthetic systems. Carbohydrate substrates are especially challenging, because of their diversity and similarity to water, the biological solvent. Here we report a synthetic receptor for glucose, which is biomimetic in both design and capabilities. The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The receptor’s affinity for glucose, at Ka ~ 18,000 M−1, compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound approximately 100 times more weakly, while non-carbohydrate substrates are ignored. Glucose-binding molecules are required for initiatives in diabetes treatment, such as continuous glucose monitoring and glucose-responsive insulin. The performance and tunability of this system augur well for such applications.

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Fig. 1: Design of glucose receptor 2.
Fig. 2: Synthetic route to receptor 2.
Fig. 3: Evidence for binding of 2 to glucose 10.
Fig. 4: Substrates and affinities for receptor 2.

Data availability

The data supporting this study are provided in the Supplementary Information and are also available from the authors upon reasonable request.


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We thank the Bristol Chemical Synthesis Doctoral Training Centre for a studentship to R.A.T., funded jointly by Ziylo and the Engineering and Physical Sciences Research Council (EP/G036764/1).

Author information




R.A.T. designed and carried out the synthetic route to receptor 2. M.G.O. and J.V.M. assisted in optimisation of the synthesis of compound 7. R.A.T. performed and analysed the binding studies, with assistance from T.S.C. and L.C. in some cases. R.A.T. and L.C. prepared the biological media. R.A.T. and M.P.C. were responsible for the structural NMR work, and H.L. performed the cytotoxicity studies. A.P.D. designed the receptor and directed the study. The paper was written by A.P.D. with input from the other authors.

Corresponding author

Correspondence to Anthony P. Davis.

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Competing interests

While this paper was under consideration, Ziylo Ltd was purchased by Novo Nordisk with a view to the development of glucose-responsive insulin. A new company Carbometrics was created to collaborate with Ziylo and explore other applications. A.P.D. was a director and shareholder of Ziylo, and is now a director and shareholder of Carbometrics. T.S.C., L.C., J.V.M. and M.G.O. were employees of Ziylo, J.V.M. and M.G.O. are now employees of Carbometrics.

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Supplementary information

Supplementary Information

Synthesis and characterization of receptor 2; synthetic methods, NMR spectra, stability and toxicity. Details of binding studies; methods and media, summary of binding results, binding data and analyses. Details of modelling studies

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Tromans, R.A., Carter, T.S., Chabanne, L. et al. A biomimetic receptor for glucose. Nature Chem 11, 52–56 (2019).

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