Anomerisation of Fluorinated Sugars by Mutarotase Studied Using 19F NMR Two-Dimensional Exchange Spectroscopy
Dmitry Shishmarev
A , Lucas Quiquempoix B , Clément Q. Fontenelle B , Bruno Linclau B and Philip W. Kuchel C D
A John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
B School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
C School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia.
D Corresponding author. Email: philip.kuchel@sydney.edu.au
Australian Journal of Chemistry 73(3) 117-128 https://doi.org/10.1071/CH19562
Submitted: 30 October 2019 Accepted: 18 November 2019 Published: 29 January 2020
Abstract
Five 19F-substituted glucose analogues were used to probe the activity and mechanism of the enzyme mutarotase by using magnetisation-exchange NMR spectroscopy. The sugars (2-fluoro-2-deoxy-d-glucose, FDG2; 3-fluoro-3-deoxy-d-glucose, FDG3; 4-fluoro-4-deoxy-d-glucose, FDG4; 2,3-difluoro-2,3-dideoxy-d-glucose, FDG23; and 2,2,3,3-tetrafluoro-2,3-dideoxy-d-glucose (2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose), FDG2233) showed separate 19F NMR spectroscopic resonances from their respective α- and β-anomers, thus allowing two-dimensional exchange spectroscopy measurements of the anomeric interconversion at equilibrium, on the time scale of a few seconds. Mutarotase catalysed the rapid exchange between the anomers of FDG4, but not the other four sugars. This finding, combined with previous work identifying the mechanism of the anomerisation by mutarotase, suggests that the rotation around the C1–C2 bond of the pyranose ring is the rate-limiting reaction step. In addition to d-glucose itself, it was shown that all other fluorinated sugars inhibited the FDG4 anomerisation, with the tetrafluorinated FDG2233 being the most potent inhibitor. Inhibition of mutarotase by F-sugars paves the way for the development of novel fluorinated compounds that are able to affect the activity of this enzyme in vitro and in vivo.
References
[1] W. Sacks, Science 1967, 158, 498.| Crossref | GoogleScholarGoogle Scholar | 4963341PubMed |
[2] W. Sacks, Arch. Biochem. Biophys. 1968, 123, 507.
| Crossref | GoogleScholarGoogle Scholar | 5661008PubMed |
[3] P. W. Kuchel, B. E. Chapman, J. R. Potts, FEBS Lett. 1987, 219, 5.
| Crossref | GoogleScholarGoogle Scholar | 3595881PubMed |
[4] R. Bentley, Annu. Rev. Biochem. 1972, 41, 953.
| Crossref | GoogleScholarGoogle Scholar | 4563446PubMed |
[5] D. J. Timson, R. J. Reece, FEBS Lett. 2003, 543, 21.
| Crossref | GoogleScholarGoogle Scholar | 12753898PubMed |
[6] H. M. Holden, I. Rayment, J. B. Thoden, J. Biol. Chem. 2003, 278, 43885.
| Crossref | GoogleScholarGoogle Scholar | 12923184PubMed |
[7] S. M. Howard, M. R. Heinrich, Arch. Biochem. Biophys. 1965, 110, 395.
| Crossref | GoogleScholarGoogle Scholar | 14342740PubMed |
[8] G. G. Bouffard, K. E. Rudd, S. L. Adhya, J. Mol. Biol. 1994, 244, 269.
| Crossref | GoogleScholarGoogle Scholar | 7966338PubMed |
[9] A. S. Keston, Anal. Biochem. 1964, 9, 228.
| Crossref | GoogleScholarGoogle Scholar | 14230700PubMed |
[10] M. Maebayashi, M. Ohba, T. Takeuchi, J. Mol. Liq. 2017, 232, 408.
| Crossref | GoogleScholarGoogle Scholar |
[11] P. W. Kuchel, B. T. Bulliman, B. E. Chapman, Biophys. Chem. 1988, 32, 89.
| Crossref | GoogleScholarGoogle Scholar | 3233317PubMed |
[12] I. P. Street, C. R. Armstrong, S. G. Withers, Biochemistry 1986, 25, 6021.
| Crossref | GoogleScholarGoogle Scholar | 3790503PubMed |
[13] C. P. S. Glaudemans, Chem. Rev. 1991, 91, 25.
| Crossref | GoogleScholarGoogle Scholar |
[14] A. Ardá, J. Jiménez-Barbero, Chem. Commun. 2018, 54, 4761.
| Crossref | GoogleScholarGoogle Scholar |
[15] J. R. Potts, A. M. Hounslow, P. W. Kuchel, Biochem. J. 1990, 266, 925.
| 2327975PubMed |
[16] J. R. Potts, P. W. Kuchel, Biochem. J. 1992, 281, 753.
| Crossref | GoogleScholarGoogle Scholar | 1536653PubMed |
[17] R. E. London, S. A. Gabel, Biophys. J. 1995, 69, 1814.
| Crossref | GoogleScholarGoogle Scholar | 8580324PubMed |
[18] T. M. O’Connell, S. A. Gabel, R. E. London, Biochemistry 1994, 33, 10985.
| Crossref | GoogleScholarGoogle Scholar | 8086416PubMed |
[19] H. W. Kim, P. Rossi, R. K. Shoemaker, S. G. DiMagno, J. Am. Chem. Soc. 1998, 120, 9082.
| Crossref | GoogleScholarGoogle Scholar |
[20] S. Bresciani, T. Lebl, A. M. Z. Slawin, D. O’Hagan, Chem. Commun. 2010, 46, 5434.
| Crossref | GoogleScholarGoogle Scholar |
[21] E. Dickinson, J. R. P. Arnold, J. Fisher, J. Biomol. NMR 2017, 67, 145.
| Crossref | GoogleScholarGoogle Scholar | 28224261PubMed |
[22] D. Shishmarev, C. Q. Fontenelle, I. Kuprov, B. Linclau, P. W. Kuchel, Biophys. J. 2018, 115, 1906.
| Crossref | GoogleScholarGoogle Scholar | 30366625PubMed |
[23] R. S. Timofte, B. Linclau, Org. Lett. 2008, 10, 3673.
| Crossref | GoogleScholarGoogle Scholar | 18671404PubMed |
[24] L. M. McIntyre, D. R. Thorburn, W. A. Bubb, P. W. Kuchel, Eur. J. Biochem. 1989, 180, 399.
| Crossref | GoogleScholarGoogle Scholar | 2924774PubMed |
[25] P. W. Kuchel, B. T. Bulliman, B. E. Chapman, G. L. Mendz, J. Magn. Reson. 1988, 76, 136.
| Crossref | GoogleScholarGoogle Scholar |
[26] D. Shishmarev, P. W. Kuchel, Biophys. Rev. 2016, 8, 369.
| Crossref | GoogleScholarGoogle Scholar | 28510013PubMed |
[27] C. L. Perrin, R. K. Gipe, J. Am. Chem. Soc. 1984, 106, 4036.
| Crossref | GoogleScholarGoogle Scholar |
[28] B. Linclau, Z. Wang, G. Compain, V. Paumelle, C. Q. Fontenelle, N. Wells, A. Weymouth-Wilson, Angew. Chem. Int. Ed. 2016, 55, 674.
| Crossref | GoogleScholarGoogle Scholar |
[29] K. E. van Straaten, J. R. A. Kuttiyatveetil, C. M. Sevrain, S. A. Villaume, J. Jiménez-Barbero, B. Linclau, S. P. Vincent, D. A. R. Sanders, J. Am. Chem. Soc. 2015, 137, 1230.
| Crossref | GoogleScholarGoogle Scholar | 25562380PubMed |
[30] J. C. Biffinger, H. W. Kim, S. G. DiMagno, ChemBioChem 2004, 5, 622.
| Crossref | GoogleScholarGoogle Scholar | 15122633PubMed |
[31] J. B. Thoden, J. Kim, F. M. Raushel, H. M. Holden, Protein Sci. 2003, 12, 1051.
| Crossref | GoogleScholarGoogle Scholar | 12717027PubMed |
[32] C. Dalvit, A. Vulpetti, Chem. – Eur. J. 2016, 22, 7592.
| Crossref | GoogleScholarGoogle Scholar | 27112430PubMed |
[33] L. A. Berven, D. H. Dolphin, S. G. Withers, J. Am. Chem. Soc. 1988, 110, 4864.
| Crossref | GoogleScholarGoogle Scholar |
[34] J. M. Bailey, P. H. Fishman, J. W. Kusiak, S. Mulhern, P. G. Pentchev, Methods Enzymol. 1975, 41, 471.
| Crossref | GoogleScholarGoogle Scholar |
[35] L. Mtashobya, L. Quiquempoix, B. Linclau, J. Fluor. Chem. 2015, 171, 92.
| Crossref | GoogleScholarGoogle Scholar |
[36] W. Lee, M. Tonelli, J. L. Markley, Bioinformatics 2015, 31, 1325.
| Crossref | GoogleScholarGoogle Scholar | 25505092PubMed |
