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. 2017 May 1;8(5):4056-4061.
doi: 10.1039/c6sc05399h. Epub 2017 Mar 30.

Enantioselective carbohydrate recognition by synthetic lectins in water

Affiliations

Enantioselective carbohydrate recognition by synthetic lectins in water

Pablo Ríos et al. Chem Sci. .

Abstract

Carbohydrate receptors with a chiral framework have been generated by combining a tetra-aminopyrene and a C3-symmetrical triamine via isophthalamide spacers bearing water-solubilising groups. These "synthetic lectins" are the first to show enantiodiscrimination in aqueous solution, binding N-acetylglucosamine (GlcNAc) with 16 : 1 enantioselectivity. They also show exceptional affinities. GlcNAc is bound with Ka up to 1280 M-1, more than twice that measured for previous synthetic lectins, and three times the value for wheat germ agglutinin, the lectin traditionally employed to bind GlcNAc in glycobiological research. Glucose is bound with Ka = 250 M-1, again higher than previous synthetic lectins. The results suggest that chirality can improve complementarity to carbohydrate substrates and may thus be advantageous in synthetic lectin design.

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Figures

Fig. 1
Fig. 1. General approach to synthetic lectins for all-equatorial carbohydrates (β-glucose, β-GlcNAc etc.), with recent achiral example 1 (see ref. 14a).
Fig. 2
Fig. 2. (a) Chiral receptor architecture derived by combining C 3 and D 2 roof/floor components. (b) Specific design 2 featured in this paper. See Scheme 1 for the structure of water-solubilising group X1. The framework of 2 is planar chiral and the enantiomer shown is pS according to standard nomenclature (see Fig. S35, ESI†).
Scheme 1
Scheme 1. Synthesis of (±)-2. (i) THF/water, 4 (8 equivalents), EtN(iPr)2, 47%; see ref. 14a. (ii) THF, EtN(iPr)2, [5] and [6] ≤ 0.11 mM, 51%. (iii) TFA, DCM. (iv) NaOH, H2O, then Amberlyst 15 hydrogen form, then NaOH (to pH = 7).
Fig. 3
Fig. 3. Selected partial spectra for a 1H NMR binding study of receptors (±)-2 (0.15 mM each) with d-GlcNAc 8 in D2O. The labelling system used for 2 and a full NMR assignment are detailed in the ESI. Signals due to protons s6a–d appear in the region 7.6–8.1 ppm and are readily observed during the titration. In particular, the signal due to s6d splits into two peaks which can be followed throughout.
Fig. 4
Fig. 4. Data analyses for the 1H NMR titration of (±)-2 with d-GlcNAc 8 (see Fig. 3) assuming a 1 : 1 binding model. The signal due to proton s6d was followed for both diastereomeric complexes. (a) Analysis of peaks marked by blue diamonds in Fig. 3 spectra; K a = 1280 M–1 ± 2%, limiting Δδ = 0.117 ppm. (b) Analysis of peaks marked by red circles in Fig. 3 spectra, K a = 81 M–1 ± 5%, limiting Δδ = 0.331 ppm.

References

    1. Davis A. P., Wareham R. S. Angew. Chem., Int. Ed. 1999;38:2978–2996. - PubMed
    2. Davis A. P. Org. Biomol. Chem. 2009;7:3629–3638. - PubMed
    3. Jin S., Cheng Y. F., Reid S., Li M. Y., Wang B. H. Med. Res. Rev. 2010;30:171–257. - PMC - PubMed
    4. Mazik M. RSC Adv. 2012;2:2630–2642.
    5. Nakagawa Y., Ito Y. Trends Glycosci. Glycotechnol. 2012;24:1–12.
    6. Miron C. E., Petitjean A. ChemBioChem. 2015;16:365–379. - PubMed
    1. See, for example:

    2. The Sugar Code-Fundamentals of Glycoscience, ed. H.-J. Gabius, Wiley-Blackwell, Weinheim, 2009.
    3. Carbohydrate Recognition: Biological Problems, Methods and Applications, ed. B. Wang and G.-J. Boons, Wiley, Hoboken, 2011.
    4. Diekman A. B. Cell. Mol. Life Sci. 2003;60:298–308. - PMC - PubMed
    5. Miller D. J., Macek M. B., Shur B. D. Nature. 1992;357:589–593. - PubMed
    6. Snell W. J., White J. M. Cell. 1996;85:629–637. - PubMed
    7. Shalgi R., Raz T. Histol. Histopathol. 1997;12:813–822. - PubMed
    8. Rubinstein E., Ziyyat A., Wolf J. P., Le Naour F., Boucheix C. Semin. Cell Dev. Biol. 2006;17:254–263. - PubMed
    9. Murrey H. E., Hsieh-Wilson L. C. Chem. Rev. 2008;108:1708–1731. - PMC - PubMed
    10. Solis D., Bovin N. V., Davis A. P., Jiménez-Barbero J., Romero A., Roy R., Smetana K., Gabius H. J. Biochim. Biophys. Acta, Gen. Subj. 2015;1850:186–235. - PubMed
    1. Caltabiano G., Campillo M., De Leener A., Smits G., Vassart G., Costagliola S., Pardo L. Cell. Mol. Life Sci. 2008;65:2484–2492. - PMC - PubMed
    1. Lau K. S., Dennis J. W. Glycobiology. 2008;18:750–760. - PubMed
    1. Buzas E. I., Gyorgy B., Pasztoi M., Jelinek I., Falus A., Gabius H. J. Autoimmunity. 2006;39:691–704. - PubMed

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