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.
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Bertuzzi, A., Mingrone, G., Gandolfi, A., Greco, A.V., Ringoir, S. and Vanholder, R. (1997) Clin. Chim. Acta, 265, 183-192.
Chen, A. and Shapiro, M.J. (1998) J. Am. Chem. Soc., 120, 10258-10259.
Chen, A. and Shapiro, M.J. (2000) J. Am. Chem. Soc., 122, 414-415.
Cheng, Y. and Prusoff, W.H. (1973) Biochem. Pharmacol., 22, 3099-3108.
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.
Dalvit, C. (1996) J. Magn. Reson., B112, 282-288.
Dalvit, C. (1998) J. Biomol. NMR, 11, 437-444.
Dalvit, C., Cottens, S., Ramage, P. and Hommel, U. (1999) J. Biomol. NMR, 13, 43-50.
Dalvit, C., Pevarello, P., Tatò, M., Veronesi, M., Vulpetti, A. and Sundström, M. (2000) J. Biomol. NMR, 18, 65-68.
Denisov, V.P. and Halle, B. (1995) J. Mol. Biol., 245, 682-697.
Denisov, V.P., Halle, B., Peters, J. and Hörlein, H.D. (1995) Biochemistry, 34, 9046-9051.
Ernst, J.A., Clubb, R.T., Zhou, H-X., Gronenborn, A.M. and Clore, G.M. (1995) Science, 267, 1813-1817.
Ernst, R.R., Bodenhausen, G. and Wokaun, A. (1997) In Principles of Nuclear Magnetic Resonance in One and Two Dimensions, Clarendon Press, Oxford.
Feeney, J., Batchelor, G., Albrand, J.P. and Roberts, G.C.K. (1979) J. Magn. Reson., 33, 519-529.
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.
Grzesiek, S. and Bax, A. (1993) J. Am. Chem. Soc., 115, 12593-12594.
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.
Hajduk, P.J., Olejniczak, E.T. and Fesik, S.W. (1997b) J. Am. Chem. Soc., 119, 12257-12261.
Halle, B. (1999) In Hydration Processes in Biology, M.-C. Bellissent-Funel (Ed.), IOS Press, Amsterdam, pp. 233-249.
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.
Henrichsen, D., Ernst, B., Magnani, J.L., Wang, W-T., Meyer, B. and Peters, T. (1999) Angew. Chem. Int. Ed., 38, 98-102.
Hwang, T-L. and Shaka, A.J. (1995) J. Magn. Reson., A112, 275-279.
Jahnke, W., Perez, L.B., Paris, C.G., Strauss, A., Fendrich, G. and Nalin, C.M. (2000) J. Am. Chem. Soc., 122, 7394-7395.
Jahnke, W., Rüdisser, S. and Zurini, M. (2001) J. Am. Chem. Soc., 123, 3149-3150.
Kalk, A. and Berendsen, H.J.C. (1976) J. Magn. Reson., 24, 343-366.
Klein, J., Meinecke, R., Mayer, M. and Meyer, B. (1999) J. Am. Chem. Soc., 121, 5336-5337.
Lepre, C.A. (2001) Drug Discovery Today, 6, 133-140.
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.
Liepinsh, E. and Otting, G. (1996) Magn. Reson. Med., 35, 30-42.
Lin, M., Shapiro, M.J. and Wareing, J.R. (1997) J Am. Chem. Soc., 119, 5249-5250.
Lin, M., Shapiro, M.J. and Wareing, J.R. (1997) J. Org. Chem., 62, 8930-8931.
Mayer, M. and Meyer, B. (1999) Angew. Chem. Int. Ed., 38, 1784-1788.
Mayer, M. and Meyer, B. (2001) J. Am. Chem. Soc., 123, 6108-6117.
McMenamy, R.H. and Oncley, J.L. (1958) J. Biol. Chem., 233, 1436-1447.
Melacini, G., Boelens, R. and Kaptein, R. (1999a) J. Biomol. NMR, 13, 67-71.
Melacini, G., Kaptein, R. and Boelens, R. (1999b) J. Magn. Reson., 136, 214-218.
Meyer, B., Weimar, T. and Peters, T. (1997) Eur. J. Biochem., 246, 705-709.
Moore, J.M. (1999) Curr. Opin. Biotechnol., 10, 54-58.
Moore, J.M. (2000) Work presented at the XIX ICMRBS August 20-25, Florence, Italy.
Otting, G. (1997) Progr. Nucl. Magn. Res. Spect., 31, 259-285, and references cited therein.
Otting, G. and Liepinsh, E. (1995) Acc. Chem. Res., 28, 171-177.
Otting, G. and Wüthrich, K. (1989) J. Am. Chem. Soc., 111, 1871-1875.
Otting, G., Liepinsh, E., Halle, B. and Frey, U. (1997) Nat. Struct. Biol., 4, 396-404.
Otting, G., Liepinsh, E. and Wüthrich, K. (1991) Science, 254, 974-980.
Poornima, C.S. and Dean, P.M. (1995) J. Comput.-Aided Mol. Des., 9, 500-512.
Shuker, S.B., Hajduk, P.J., Meadows, R.P. and Fesik, S.W. (1996) Science, 274, 1531-1534.
Stockman, B.J. (1998) Progr. Nucl. Magn. Res. Spect., 33, 109-151.
Stoesz, J.D. and Redfield, A.G. (1978) FEBS Lett., 91, 320-324.
Stott, K., Keeler, J., Van, Q.N. and Shaka, A.J. (1997) J. Magn. Reson., 125, 302-324.
Vijayakumar, M., Wong, K.-Y., Schreiber, G., Fersht, A.R., Szabo, A. and Zhou, H.-X. (1998) J. Mol. Biol., 278, 1015-1024.
Wider, G. (1998) Progr. Nucl. Magn. Res. Spectr., 32, 193-273, and references cited therein.
Wiesner, S., Kurian, E., Prendergast, F.G. and Halle, B. (1999) J. Mol. Biol., 286, 233-246.
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.
Wüthrich, K. (1986) NMR of Proteins and Nucleic Acids, John Wiley and Sons, New York, NY.
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Dalvit, C., Fogliatto, G., Stewart, A. et al. WaterLOGSY as a method for primary NMR screening: Practical aspects and range of applicability. J Biomol NMR 21, 349–359 (2001). https://doi.org/10.1023/A:1013302231549
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DOI: https://doi.org/10.1023/A:1013302231549