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A simple and accessible synthetic lectin for glucose recognition and sensing

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.

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Figure 1: Synthetic lectins: old and new designs.
Figure 2: Synthetic route to the control macrocycle 9.
Figure 3
Figure 4: Data from binding studies on 5 + glucose.
Figure 5: NMR-based structure for the complex of 5 with methyl β-D-glucoside 10.

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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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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.

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Correspondence to Anthony P. Davis.

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The authors declare no competing financial interests.

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Ke, C., Destecroix, H., Crump, M. et al. A simple and accessible synthetic lectin for glucose recognition and sensing. Nature Chem 4, 718–723 (2012). https://doi.org/10.1038/nchem.1409

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