Journal of Biomolecular NMR

, Volume 21, Issue 4, pp 349–359 | Cite as

WaterLOGSY as a method for primary NMR screening: Practical aspects and range of applicability

  • Claudio Dalvit
  • GianPaolo Fogliatto
  • Albert Stewart
  • Marina Veronesi
  • Brian Stockman

Abstract

WaterLOGSY represents a powerful method for primary NMR screening in the identification of compounds interacting with macromolecules, including proteins and DNA or RNA fragments. Several relay pathways are used constructively in the experiment for transferring bulk water magnetization to the ligand. The method is particularly useful for the identification of novel scaffolds of micromolar affinity that can be then optimized using directed screening, combinatorial chemistry, medicinal chemistry and structure-based drug design. The practical aspects and range of applicability of the WaterLOGSY experiment are analyzed in detail here. Competition binding and titration WaterLOGSY permit, after proper correction, the evaluation of the dissociation binding constant. The high sensitivity of the technique in combination with the easy deconvolution of the mixtures for the identification of the active components, significantly reduces the amount of material and time needed for the NMR screening process.

dissociation binding constant drug design magnetization transfer NMR screening protein-ligand interactions Water-Ligand Observed via Gradient SpectroscopY WaterLOGSY 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bertuzzi, A., Mingrone, G., Gandolfi, A., Greco, A.V., Ringoir, S. and Vanholder, R. (1997) Clin. Chim. Acta, 265, 183-192.Google Scholar
  2. Chen, A. and Shapiro, M.J. (1998) J. Am. Chem. Soc., 120, 10258-10259.Google Scholar
  3. Chen, A. and Shapiro, M.J. (2000) J. Am. Chem. Soc., 122, 414-415.Google Scholar
  4. Cheng, Y. and Prusoff, W.H. (1973) Biochem. Pharmacol., 22, 3099-3108.Google Scholar
  5. Connely, P.R. (1997) In Structure-Based Drug Design Thermodynamics, Modeling and Strategy, J.E. Ladbury and P.R. Connely (Eds.), Springer-Verlag and Landes Bioscience, Berlin, pp. 143-159.Google Scholar
  6. Dalvit, C. (1996) J. Magn. Reson., B112, 282-288.Google Scholar
  7. Dalvit, C. (1998) J. Biomol. NMR, 11, 437-444.Google Scholar
  8. Dalvit, C., Cottens, S., Ramage, P. and Hommel, U. (1999) J. Biomol. NMR, 13, 43-50.Google Scholar
  9. Dalvit, C., Pevarello, P., Tatò, M., Veronesi, M., Vulpetti, A. and Sundström, M. (2000) J. Biomol. NMR, 18, 65-68.Google Scholar
  10. Denisov, V.P. and Halle, B. (1995) J. Mol. Biol., 245, 682-697.Google Scholar
  11. Denisov, V.P., Halle, B., Peters, J. and Hörlein, H.D. (1995) Biochemistry, 34, 9046-9051.Google Scholar
  12. Ernst, J.A., Clubb, R.T., Zhou, H-X., Gronenborn, A.M. and Clore, G.M. (1995) Science, 267, 1813-1817.Google Scholar
  13. Ernst, R.R., Bodenhausen, G. and Wokaun, A. (1997) In Principles of Nuclear Magnetic Resonance in One and Two Dimensions, Clarendon Press, Oxford.Google Scholar
  14. Feeney, J., Batchelor, G., Albrand, J.P. and Roberts, G.C.K. (1979) J. Magn. Reson., 33, 519-529.Google Scholar
  15. Fejzo, J., Lepre, C.A., Peng, J.W., Bemis, G.W., Ajay, Murcko, M.A. and Moore, J.M. (1999) Chemistry Biol., 6, 755-769.Google Scholar
  16. Grzesiek, S. and Bax, A. (1993) J. Am. Chem. Soc., 115, 12593-12594.Google Scholar
  17. Hajduk, P.J., Sheppard, D.G., Nettesheim, D.G., Olejniczak, E.T., Shuker, S.B., Meadows, R.P., Steinman, D.H., Carrera, G.M. Jr., Marcotte, P.M., Severin, J., Walter, K., Smith, H., Gubbins, E., Simmer, R., Holzman, T.F., Morgan, D.W., Davidsen, S.K., Summers, J.B. and Fesik, S.W. (1997a) J Am. Chem. Soc., 119, 5818-5827.Google Scholar
  18. Hajduk, P.J., Olejniczak, E.T. and Fesik, S.W. (1997b) J. Am. Chem. Soc., 119, 12257-12261.Google Scholar
  19. Halle, B. (1999) In Hydration Processes in Biology, M.-C. Bellissent-Funel (Ed.), IOS Press, Amsterdam, pp. 233-249.Google Scholar
  20. Halle, B., Denisov, V.P. and Venu, K. (1999) In Biological Magnetic Resonance, Volume 17, Structure Computation and Dynamics in Protein NMR, Krishna and Berliner (Eds.), Kluwer Academic Publishers/Plenum Publishers, New York, NY, pp. 419-484, and references cited therein.Google Scholar
  21. Henrichsen, D., Ernst, B., Magnani, J.L., Wang, W-T., Meyer, B. and Peters, T. (1999) Angew. Chem. Int. Ed., 38, 98-102.Google Scholar
  22. Hwang, T-L. and Shaka, A.J. (1995) J. Magn. Reson., A112, 275-279.Google Scholar
  23. Jahnke, W., Perez, L.B., Paris, C.G., Strauss, A., Fendrich, G. and Nalin, C.M. (2000) J. Am. Chem. Soc., 122, 7394-7395.Google Scholar
  24. Jahnke, W., Rüdisser, S. and Zurini, M. (2001) J. Am. Chem. Soc., 123, 3149-3150.Google Scholar
  25. Kalk, A. and Berendsen, H.J.C. (1976) J. Magn. Reson., 24, 343-366.Google Scholar
  26. Klein, J., Meinecke, R., Mayer, M. and Meyer, B. (1999) J. Am. Chem. Soc., 121, 5336-5337.Google Scholar
  27. Lepre, C.A. (2001) Drug Discovery Today, 6, 133-140.Google Scholar
  28. Lian, L.Y. and Roberts, G.C.K. (1993) In NMR of Macromolecules, G.C.K. Roberts (Ed.), Oxford University Press, Oxford, pp. 153-182.Google Scholar
  29. Liepinsh, E. and Otting, G. (1996) Magn. Reson. Med., 35, 30-42.Google Scholar
  30. Lin, M., Shapiro, M.J. and Wareing, J.R. (1997) J Am. Chem. Soc., 119, 5249-5250.Google Scholar
  31. Lin, M., Shapiro, M.J. and Wareing, J.R. (1997) J. Org. Chem., 62, 8930-8931.Google Scholar
  32. Mayer, M. and Meyer, B. (1999) Angew. Chem. Int. Ed., 38, 1784-1788.Google Scholar
  33. Mayer, M. and Meyer, B. (2001) J. Am. Chem. Soc., 123, 6108-6117.Google Scholar
  34. McMenamy, R.H. and Oncley, J.L. (1958) J. Biol. Chem., 233, 1436-1447.Google Scholar
  35. Melacini, G., Boelens, R. and Kaptein, R. (1999a) J. Biomol. NMR, 13, 67-71.Google Scholar
  36. Melacini, G., Kaptein, R. and Boelens, R. (1999b) J. Magn. Reson., 136, 214-218.Google Scholar
  37. Meyer, B., Weimar, T. and Peters, T. (1997) Eur. J. Biochem., 246, 705-709.Google Scholar
  38. Moore, J.M. (1999) Curr. Opin. Biotechnol., 10, 54-58.Google Scholar
  39. Moore, J.M. (2000) Work presented at the XIX ICMRBS August 20-25, Florence, Italy.Google Scholar
  40. Otting, G. (1997) Progr. Nucl. Magn. Res. Spect., 31, 259-285, and references cited therein.Google Scholar
  41. Otting, G. and Liepinsh, E. (1995) Acc. Chem. Res., 28, 171-177.Google Scholar
  42. Otting, G. and Wüthrich, K. (1989) J. Am. Chem. Soc., 111, 1871-1875.Google Scholar
  43. Otting, G., Liepinsh, E., Halle, B. and Frey, U. (1997) Nat. Struct. Biol., 4, 396-404.Google Scholar
  44. Otting, G., Liepinsh, E. and Wüthrich, K. (1991) Science, 254, 974-980.Google Scholar
  45. Poornima, C.S. and Dean, P.M. (1995) J. Comput.-Aided Mol. Des., 9, 500-512.Google Scholar
  46. Shuker, S.B., Hajduk, P.J., Meadows, R.P. and Fesik, S.W. (1996) Science, 274, 1531-1534.Google Scholar
  47. Stockman, B.J. (1998) Progr. Nucl. Magn. Res. Spect., 33, 109-151.Google Scholar
  48. Stoesz, J.D. and Redfield, A.G. (1978) FEBS Lett., 91, 320-324.Google Scholar
  49. Stott, K., Keeler, J., Van, Q.N. and Shaka, A.J. (1997) J. Magn. Reson., 125, 302-324.Google Scholar
  50. Vijayakumar, M., Wong, K.-Y., Schreiber, G., Fersht, A.R., Szabo, A. and Zhou, H.-X. (1998) J. Mol. Biol., 278, 1015-1024.Google Scholar
  51. Wider, G. (1998) Progr. Nucl. Magn. Res. Spectr., 32, 193-273, and references cited therein.Google Scholar
  52. Wiesner, S., Kurian, E., Prendergast, F.G. and Halle, B. (1999) J. Mol. Biol., 286, 233-246.Google Scholar
  53. Williamson, J.R. (2000) Work presented at the Cambridge Healthtech Institute NMR Drug Discovery and Design-Post Genomic Analysis October 24-26, McLean, VA, U.S.A.Google Scholar
  54. Wüthrich, K. (1986) NMR of Proteins and Nucleic Acids, John Wiley and Sons, New York, NY.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Claudio Dalvit
    • 1
  • GianPaolo Fogliatto
    • 2
  • Albert Stewart
    • 2
  • Marina Veronesi
    • 1
  • Brian Stockman
    • 3
  1. 1.ChemistryItaly
  2. 2.Biology Department, PharmaciaNervianoItaly
  3. 3.Structural, Analytical & Medicinal Chemistry DepartmentPharmaciaKalamazooU.S.A

Personalised recommendations