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A simple and accessible synthetic lectin for glucose recognition and sensing

Nature Chemistry volume 4, pages 718–723 (2012)Cite this article

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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.

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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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References

  1. Davis, A. P. & Wareham, R. S. Carbohydrate recognition through noncovalent interactions: a challenge for biomimetic and supramolecular chemistry. Angew. Chem. Int. Ed. 38, 2978–2996 (1999).

    Article  CAS  Google Scholar 

  2. Striegler, S. Selective carbohydrate recognition by synthetic receptors in aqueous solution. Curr. Org. Chem. 7, 81–102 (2003).

    Article  CAS  Google Scholar 

  3. Toone, E. J. Structure and energetics of protein–carbohydrate complexes. Curr. Opin. Struct. Biol. 4, 719–728 (1994).

    Article  CAS  Google Scholar 

  4. Ambrosi, M., Cameron, N. R. & Davis, B. G. Lectins: tools for the molecular understanding of the glycocode. Org. Biomol. Chem. 3, 1593–1608 (2005).

    Article  CAS  Google Scholar 

  5. Gabius, H-J. The Sugar Code – Fundamentals of Glycoscience (Wiley-Blackwell, 2009).

    Google Scholar 

  6. Wang, B. & Boons, G-J. Carbohydrate Recognition: Biological Problems, Methods and Applications (Wiley, 2011).

    Book  Google Scholar 

  7. Balzarini, J. Targeting the glycans of glycoproteins: a novel paradigm for antiviral therapy. Nature Rev. Microbiol. 5, 583–597 (2007).

    Article  CAS  Google Scholar 

  8. Jin, S., Cheng, Y. F., Reid, S., Li, M. Y. & Wang, B. H. Carbohydrate recognition by boronolectins, small molecules, and lectins. Med. Res. Rev. 30, 171–257 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Katrlik, J., Svitel, J., Gemeiner, P., Kozar, T. & Tkac, J. Glycan and lectin microarrays for glycomics and medicinal applications. Med. Res. Rev. 30, 394–418 (2010).

    CAS  PubMed  Google Scholar 

  10. Kubik, S. Synthetic lectins. Angew. Chem. Int. Ed. 48, 1722–1725 (2009).

    Article  CAS  Google Scholar 

  11. Davis, A. P. Synthetic lectins. Org. Biomol. Chem. 7, 3629–3638 (2009).

    Article  CAS  Google Scholar 

  12. Mazik, M. & Cavga, H. Carboxylate-based receptors for the recognition of carbohydrates in organic and aqueous media. J. Org. Chem. 71, 2957–2963 (2006).

    Article  CAS  Google Scholar 

  13. Pal, A., Berube, M. & Hall, D. G. Synthesis, and screening of a library of peptidyl bis(boroxoles) as oligosaccharide receptors in water: identification of a receptor for the tumor marker TF-antigen disaccharide. Angew. Chem. Int. Ed. 49, 1492–1495 (2010).

    Article  CAS  Google Scholar 

  14. Rauschenberg, M., Bomke, S., Karst, U. & Ravoo, B. J. Dynamic peptides as biomimetic carbohydrate receptors. Angew. Chem. Int. Ed. 49, 7340–7345 (2010).

    Article  CAS  Google Scholar 

  15. Klein, E., Crump, M. P. & Davis, A. P. Carbohydrate recognition in water by a tricyclic polyamide receptor. Angew. Chem. Int. Ed. 44, 298–302 (2005).

    Article  CAS  Google Scholar 

  16. Ferrand, Y., Crump, M. P. & Davis, A. P. A synthetic lectin analog for biomimetic disaccharide recognition. Science 318, 619–622 (2007).

    Article  CAS  Google Scholar 

  17. Ferrand, Y. et al. A synthetic lectin for O-linked beta-N-acetylglucosamine. Angew. Chem. Int. Ed. 48, 1775–1779 (2009).

    Article  CAS  Google Scholar 

  18. Barwell, N. P., Crump, M. P. & Davis, A. P. A synthetic lectin for beta-glucosyl. Angew. Chem. Int. Ed. 48, 7673–7676 (2009).

    Article  CAS  Google Scholar 

  19. Vyas, N. K., Vyas, M. N. & Quiocho, F. A. Sugar and signal-transducer binding sites of the Escherichia coli galactose chemoreceptor protein. Science 242, 1290–1295 (1988).

    Article  CAS  Google Scholar 

  20. Solis, D., Romero, A., Menendez, M. & Jiménez-Barbero, J. in The Sugar Code – Fundamentals of Glycoscience (Gabius, H-J. ed.) 233–245 (Wiley-Blackwell, 2009).

    Google Scholar 

  21. Nishio, M. The CH/pi hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates. Phys. Chem. Chem. Phys. 13, 13873–13900 (2011).

    Article  CAS  Google Scholar 

  22. Chavez, M. I. et al. On the importance of carbohydrate–aromatic interactions for the molecular recognition of oligosaccharides by proteins: NMR studies of the structure and binding affinity of AcAMP2-like peptides with non-natural naphthyl and fluoroaromatic residues. Chem. Eur. J. 11, 7060–7074 (2005).

    Article  CAS  Google Scholar 

  23. Laughrey, Z. R., Kiehna, S. E., Rierrien, A. J. & Waters, M. L. Carbohydrate-pi interactions: what are they worth? J. Am. Chem. Soc. 130, 14625–14633 (2008).

    Article  CAS  Google Scholar 

  24. Lemieux, R. U. How water provides the impetus for molecular recognition in aqueous solution. Acc. Chem. Res. 29, 373–380 (1996).

    Article  CAS  Google Scholar 

  25. Klein, E., Ferrand, Y., Barwell, N. R. & Davis, A. P. Solvent effects in carbohydrate binding by synthetic receptors: implications for the role of water in natural carbohydrate recognition. Angew. Chem. Int. Ed. 47, 2693–2696 (2008).

    Article  CAS  Google Scholar 

  26. Gassensmith, J. J. et al. Self-assembly of fluorescent inclusion complexes in competitive media including the interior of living cells. J. Am. Chem. Soc. 129, 15054–15059 (2007).

    Article  CAS  Google Scholar 

  27. Billing, J., Grundberg, H. & Nilsson, U. J. Amphiphilic anthracene–amino acid conjugates as simple carbohydrate receptors in water. Supramol. Chem. 14, 367–372 (2002).

    Article  CAS  Google Scholar 

  28. Miller, M. W., Amidon, R. W. & Tawney, P. O. Some meso-substituted anthracenes. 1. 9,10-Bis-(chloromethyl)-anthracene as a synthetic intermediate. J. Am. Chem. Soc. 77, 2845–2848 (1955).

    Article  CAS  Google Scholar 

  29. Gunnlaugsson, T., Davis, A. P., O'Brien, J. E. & Glynn, M. Fluorescent sensing of pyrophosphate and bis-carboxylates with charge neutral PET chemosensors. Org. Lett. 4, 2449–2452 (2002).

    Article  CAS  Google Scholar 

  30. Huang, C. Y. Determination of binding stoichiometry by the continuous variation method – the Job plot. Methods Enzymol. 87, 509–525 (1982).

    Article  CAS  Google Scholar 

  31. Meyer, E. A., Castellano, R. K. & Diederich, F. Interactions with aromatic rings in chemical and biological recognition. Angew. Chem. Int. Ed. 42, 1210–1250 (2003).

    Article  CAS  Google Scholar 

  32. Davis, A. P. & Wareham, R. S. A tricyclic polyamide receptor for carbohydrates in organic media. Angew. Chem. Int. Ed. 37, 2270–2273 (1998).

    Article  Google Scholar 

  33. Chi, L., Zhao, J. Z. & James, T. D. Chiral mono boronic acid as fluorescent enantioselective sensor for mono alpha-hydroxyl carboxylic acids. J. Org. Chem. 73, 4684–4687 (2008).

    Article  CAS  Google Scholar 

  34. Bosch, L. I., Fyles, T. M. & James, T. D. Binary and ternary phenylboronic acid complexes with saccharides and Lewis bases. Tetrahedron 60, 11175–11190 (2004).

    Article  CAS  Google Scholar 

  35. James, T. D., Phillips, M. D. & Shinkai, S. Boronic Acids in Saccharide Recognition (Royal Society of Chemistry, 2006).

    Google Scholar 

  36. Steiner, M. S., Duerkop, A. & Wolfbeis, O. S. Optical methods for sensing glucose. Chem. Soc. Rev. 40, 4805–4839 (2011).

    Article  CAS  Google Scholar 

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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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Authors and 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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  1. Chenfeng Ke
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  2. Harry Destecroix
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  4. 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.

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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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