Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The solution conformation of sialyl-α(2→6)-lactose studied by modern NMR techniques and Monte Carlo simulations

  • 212 Accesses

  • 116 Citations

Summary

We present a comprehensive strategy for detailed characterization of the solution conformations of oligosaccharides by NMR spectroscopy and force-field calculations. Our experimental strategy generates a number of interglycosidic spatial constraints that is sufficiently large to allow us to determine glycosidic linkage conformations with a precision heretofore unachievable. In addition to the commonly used {1H,1H} NOE contacts between aliphatic protons, our constraints are: (a) homonuclear NOEs of hydroxyl protons in H2O to other protons in the oligosaccharide, (b) heteronuclear {1H,13C} NOEs, (c) isotope effects of O1H/O2H hydroxyl groups on13C chemical shifts, and (d) long-range heteronuclear scalar coupling across glycosidic bonds.

We have used this approach to study the trisaccharide sialyl-α(2→6)-lactose in aqueous solution. The experimentally determined geometrical constraints were compared to results obtained from force-field calculations based on Metropolis Monte Carlo simulations. The molecule was found to exist in 2 families of conformers. The preferred conformations of the α(2→6)-linkage of the trisaccharide are best described by an equilibrium of 2 conformers with Φ angles at −60° or 180° and of the 3 staggered rotamers of the Ω angle with a predominantgt conformer. Three intramolecular hydrogen bonds, involving the hydroxyl protons on C8 and C7 of the sialic acid residue and on C3 of the reducing-end glucose residue, contribute significantly to the conformational stability of the trisaccharide in aqueous solution.

This is a preview of subscription content, log in to check access.

References

  1. Acquotti, D., Poppe, L., Dabrowski, J., Von der Lieth, C.W., Sonnino, S. and Tettamanti, G. (1990)J. Am. Chem. Soc.,112, 7772–7778.

  2. Bax, A. (1988).J. Magn. Reson.,77, 134–147.

  3. Bax, A. and Davis, D.G. (1985)J. Magn. Reson.,63, 207–213.

  4. Ben-Naim, A., Ting, K.L. and Jernigan, R.L. (1990)Biopolymers,29, 901–919.

  5. Berman, E. (1984)Biochemistry,23, 3754–3759.

  6. Bock, K. (1983)Pure Appl. Chem.,55, 605–622.

  7. Bothner-By, A.A. and Shukla, R. (1988)J. Magn. Reson.,77, 524–535.

  8. Bothner-By, A.A., Stephens, R.L., Lee, J., Warren, C.D. and Jeanloz, R.W. (1984)J. Am. Chem. Soc.,106, 428–429.

  9. Boudot, D., Canet, D., Brondeau, J. and Boubel, J.C. (1989)J. Magn. Reson.,83, 428–439.

  10. Brady, J.W. (1989)J. Am. Chem. Soc.,111, 5155–5165.

  11. Braunschweiler, L. and Ernst, R.R. (1983)J. Magn. Reson.,53, 521–528.

  12. Breg, J., Kroon-Batenburg, L.M.J., Strecker, G., Montreuil, J. and Vliegenthart, J.F.G. (1989)Eur. J. Biochem.,178, 727–739.

  13. Brown, E.B., Brey, W.S. and Weltner, W. Jr. (1975)Biochim. Biophys. Acta. 399, 124–130.

  14. Bush, C.A. (1988)Bull. Magn. Reson.,10, 73–95.

  15. Carver, J.P., Mandel, D., Michnick, S.W., Imberty, A. and Brady, J.W. (1990)ACS Symp. Ser.,430, 266–280.

  16. Casu, B., Reggiani, M., Gallo, G.G. and Vigevani, A. (1966)Tetrahedron.22, 3061–3083.

  17. Christofides, J.C., Davies, D.B., Martin, J.A. and Rathbone, E.B. (1986)J. Am. Chem. Soc.,108, 5738–5743.

  18. Chu, S.S.C. and Jeffrey, G.A. (1968)Acta Crystallogr., Sect. B. 24, 830–838.

  19. Cumming, D.A. and Carver, J.P. (1987)Biochemistry,26, 6676–6683.

  20. Dabrowski, J. and Poppe, L. (1989)J. Am. Chem. Soc.,111, 1510–1511.

  21. Edge, C.J., Singh, U.C., Bazzo, R., Taylor, G.L., Dwek, R.A. and Rademacher, T.W. (1990)Biochemistry,29, 1971–1974.

  22. Farmer, B.T., II, Macura, S. and Brown, L.R. (1987)J. Magn. Resons.,72, 347–352.

  23. Fejzo, J., Zolnai, Z., Macura, S. and Markley, J.L. (1989)J. Magn. Reson.,82, 518–528.

  24. French, A.D. (1988)Biopolymers,27, 1519–1525.

  25. Geen, H., Wu, X.L., Friedrich, J. and Freeman, R. (1989)J. Magn. Reson.,81, 646–652.

  26. Ha, S.N., Giammona, A., Field, M. and Brady, J.W. (1988)Carbohydr. Res.,180, 207–221.

  27. Haasnoot, C.A.G., De Leeuw, F.A.A.M. and Altona, C. (1980)Tetrahedron,36, 2783–2792.

  28. Hills, B.P. (1991)Mol. Phys.,72, 1099–1121.

  29. Homans, S.W. (1990a)Progr. NMR Spectrosc.,22, 55–81.

  30. Homans, S.W. (1990b)Biochemistry,29, 9110–9118.

  31. Homans, S.W., Dwek, R.A., Boyd, J., Mahmoudian, M., Richards, W.G. and Rademacher, T.W. (1986)Biochemistry,25, 6342–6350.

  32. Homans, S.W., Dwek, R.A. and Rademacher, T.W. (1987)Biochemistry,26, 6571–6578.

  33. Hoult, D.J. and Richards, R.E. (1975)Proc. Royal Soc. London,344, 311–319.

  34. Imberty, A., Gerber, S., Tran, V. and Pérez, S. (1990)Glycoconjugate J.,7, 27–54.

  35. Jeffrey, G.A. (1990)ACS Symp. Ser.,430, 20–30.

  36. Karplus, M. (1959)J. Chem. Phys.,30, 11–15.

  37. Kessler, H., Gemmecker, G. and Haase, B. (1988)J. Magn. Reson.,77, 401–408.

  38. Lemieux, R.U. (1989)Chem. Soc. Rev.,18, 347–374.

  39. Lemieux, R.U. and Bock, K. (1984)Jpn. J. Antibiot. Suppl.,32, 163–167.

  40. Lemieux, R.U., Bock, K., Delbaere, L.T.J., Koto, S. and Rao, V.S. (1980)Can. J. Chem. 58, 631–653.

  41. Lerner, L. and Bax, A. (1987)Carbohydr. Res.,166, 35–46.

  42. Marion, D. and Wüthrich, K. (1983).Biochem. Biophys. Res. Commun.,113, 967–974.

  43. Metropolis, N., Rosenbluth, A.W., Rosenbluth, M.N., Teller, A.H. and Teller, E. (1953)J. Chem. Phys.,21, 1087–1092.

  44. Meyer, B. (1990)Top. Curr. Chem.,154, 141–208.

  45. Meyer, B., Zsiska, M. and Stuike-Prill, R. (1992) InComputer Simulation Studies in Condensed Matter Physics (Eds, Landau, D.P., Mon, K.K. and Schuttler, H.B.) Vol. IV, Springer, Heidelberg, in press.

  46. Morris, G.A. and Freeman, R. (1978).J. Magn. Reson.,29, 433–462.

  47. Müller, L. (1979)J. Am. Chem. Soc.,101, 4481–4482.

  48. Mulloy, B., Frenkiel, T.A. and Davies, D.B. (1988)Carbohydr. Res.,184, 39–46.

  49. Neuhaus, D. and Williamson, M.P. (1989)The Nuclear Overhauser Effects in Structural and Conformational Analysis. VCH Publishers, New York.

  50. Ohrui, H., Nishida, Y., Watanabe, M., Hori, H. and Meguro, H. (1985)Tetrahedron Lett.,26, 3251–3254.

  51. Ohrui, H., Nishida, Y., Itoh, H. and Meguro, H. (1991)J. Org. Chem.,56, 1726–1731.

  52. Otting, G. and Wüthrich, K. (1988)J. Magn. Reson.,76, 569–574.

  53. Peters, T., Meyer, B., Stuike-Prill, R., Somorjai, R., and Brisson, J.R. (1992)Biochemistry, in press.

  54. Platzer, N., Davoust, D., Lhermitte, M., Bauvy, C., Meyer, D.M. and Derappe, C. (1989)Carbohydr. Res.,191, 191–207.

  55. Poppe, L. and Dabrowski, J. (1989)Biochem. Biophys. Res. Commun. 159, 618–623.

  56. Poppe, L., Dabrowski, J., Von der Lieth, C.W., Numata, M. and Ogawa, T. (1989)Eur. J. Biochem.,180, 337–342.

  57. Poppe, L., Von der Lieth, C.W. and Dabrowski, J. (1990a)J. Am. Chem. Soc.,112, 7762–7771.

  58. Poppe, L., Dabrowski, J., Von der Lieth, C.W., Koike, K. and Ogawa, T. (1990b)Eur. J. Biochem.,189, 313–325.

  59. Poppe, L. and Van Halbeck, H. (1991a)J. Am. Chem. Soc.,113, 363–365.

  60. Poppe, L. and Van Halbeek, H. (1991b)Magn. Reson. Chem.,29, 355–361.

  61. Poppe, L. and Van Halbeek, H. (1991c)J. Magn. Reson.,92, 636–641.

  62. Poppe, L. and Van Halbeek, H. (1991d)J., Magn. Reson.,93, 214–217.

  63. Poppe, L. and Van Halbeck, H. (1991e)Magn. Reson. Chem.,29, 848–851.

  64. Poppe, L. and Van Halbeek, H. (1991f)Glycoconjugate J.,8, 130.

  65. Rademacher, T.W., Parekh, R.B. and Dwek, R.A. (1988)Annu. Rev. Biochem.,57, 785–838.

  66. Ram, P., Mazzola, L. and Prestegard, J.H. (1989).J. Am. Chem. Soc.,111, 3176–3182.

  67. Rasmussen, K. (1983)J. Mol. Struct.,97, 53–56.

  68. Rees, D.A. and Smith, P.J.C. (1975)J. Chem. Soc. Perkin II, 830–835.

  69. Reuben, J. (1984)J. Am. Chem. Soc.,106, 6180–6186.

  70. Scarsdale, J.N., Ram, P., Prestegard, J.H. and Yu, R.K. (1988)J. Comput. Chem.,9, 133–147.

  71. Schauer, R. (1982)Adv. Carbohydr. Chem. Biochem.,40, 131–234.

  72. Sklenar, V. and Bax, A. (1987)J. Am. Chem. Soc.,74, 469–479.

  73. Sklenar, V. and Feigon, J. (1990)J. Am. Chem. Soc.,112, 5644–5645.

  74. Spoormaker, T. and De Bie, M.J.A. (1978)Recl. Trav. Chim. Pays-Bas. 97, 61–90.

  75. Stuike-Prill, R. and Meyer, B. (1990)Eur. J. Biochem.,194, 903–919.

  76. Stukke-Prill, R. and Meyer, B. (1991)Carbohydr. Res., submitted.

  77. Subramanian, S. and Bax, A. (1987)J. Magn. Reson.,71, 325–330.

  78. Thogersen, H., Lemieux, R.U., Bock, K. and Meyer, B. (1982)Can. J. Chem.,60, 44–57.

  79. Tropp, J. (1980)J. Chem. Phys.,72, 6035–6047.

  80. Tvaroska, I., Hricovini, M. and Petráková, E. (1989)Carbohydr. Res.,189, 359–362.

  81. Tvaroska, I. (1990)Carbohydr. Res.,206, 55–64.

  82. Van Halbeek, H. and Poppe, L. (1991)Abstr. 10th International Meeting on NMR Spectroscopy. St. Andrews, Scotland, July 8 12, 1991, p. O 10.

  83. Wennerström, H. (1972)Mol. Phys. 24, 69–80.

  84. Wiberg, K.B. and Murcko, M.A. (1989)J. Am. Chem. Soc.,111, 4821–4828.

  85. Wu, X.L., Xu, P., Friedrich, J. and Freeman, R. (1989)J. Magn. Reson.,81, 206–211.

  86. Wüthrich, K. (1986)NMR of proteins and nucleic acids. Wiley, New York.

  87. Yan, Z.Y. and Bush, C.A. (1990)Biopolymers,29, 799–811.

Download references

Author information

Correspondence to Herman van Halbeek.

Additional information

Supplementary material available from the corresponding author: Table containing values for the dihedral angles Φ, Ψ, Ω, Θ, and for bond angles τ, for the six lowest-energy conformations of sialyl-α(2→6)-lactose (1 page).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Poppe, L., Stuike-Prill, R., Meyer, B. et al. The solution conformation of sialyl-α(2→6)-lactose studied by modern NMR techniques and Monte Carlo simulations. J Biomol NMR 2, 109–136 (1992). https://doi.org/10.1007/BF01875524

Download citation

Keywords

  • Oligosaccharide
  • Hydroxyl proton
  • Selective 3D NMR
  • Long-range {1H,13C}J-coupling
  • Metropolis Monte Carlo simulation