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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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).
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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Tromans, R.A., Carter, T.S., Chabanne, L. et al. A biomimetic receptor for glucose. Nature Chem 11, 52–56 (2019). https://doi.org/10.1038/s41557-018-0155-z
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