NMR in drug discovery

Nature Reviews Drug Discovery

Volumn 1, Issue 3, 2002, Pages 211-219

  Pellecchia, Maurizio ^a   Sem, Daniel S ^a   Wüthrich, Kurt ^b,c  

^a Triad Therapeutics Inc   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; DRUG; PROTON; PROTEIN;

BINDING AFFINITY; BINDING SITE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DRUG DESIGN; DRUG RESEARCH; DRUG STRUCTURE; LIGAND BINDING; MOLECULAR INTERACTION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUCLEAR OVERHAUSER EFFECT; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FAMILY; PROTON NUCLEAR MAGNETIC RESONANCE; REVIEW; STRUCTURE ACTIVITY RELATION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; PROTEIN CONFORMATION;

DRUG DESIGN; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PHARMACEUTICAL PREPARATIONS; PROTEIN CONFORMATION; PROTEINS;

EID: 0036490372     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd748     Document Type: Review

References (47)

1. Wüthrich, K. NMR of Proteins and Nucleic Acids. (Wiley, New York, 1986).
2. Pellecchia, M. et al. NMR-based structural characterization of large protein-ligand interactions. J. Biomol. NMR 22, 165-173 (2002).
3. Medek, A., Hajduk, P. J., Mack, J. & Fesik, S. W. The use of differential chemical shift for determining the binding site location and orientation of protein-bound ligands. J. Am. Chem. Soc. 122, 1241-1242 (2000).
4. Abragam, A. Principles of Nuclear Magnetism (Oxford Univ. Press, New York, 1961).
5. Neuhaus, D. & Williamson, M. P. The Nuclear Overhauser Effect in Structural and Conformational Analysis. (Wiley-VCH, New York, 2000).
6. Kumar, A., Ernst, R. R. & Wüthrich, K. A two-dimensional nuclear Overhauser enhancement (2D NOE) experiment for the elucidation of complete proton-proton cross-relaxation networks in biological macromolecules. Biochem. Biophys. Res. Commun. 95, 1-6 (1980).
7. Hajduk, P. J., Olejniczak, E. T. & Fesik, S. W. One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules. J. Am. Chem. Soc. 119, 12257-12261 (1997).
8. Jahnke, W., Rüdisser, S. & Zurini, M. Spin label enhanced NMR screening. J. Am. Chem. Soc. 123, 3149-3150 (2001).
9. Ni, F. Recent developments in transferred NOE methods. Prog. NMR Spectrosc. 26, 517-606 (1994).
10. Mayer, M. & Meyer, B. Characterization of ligand binding by saturation transfer difference NMR spectroscopy. Angew. Chem. Int. Edn Engl. 38, 1784-1788 (1999).
11. Klein, J., Meinecke, R., Mayer, M. & Meyer, B. Detecting binding affinity to immobilized receptor proteins in compound libraries by HR-MAS STD NMR. J. Am. Chem. Soc. 121, 5336-5337 (1999).
12. Chen, A. & Shapiro, M. J. NOE pumping: a novel NMR technique for identification of compounds with binding affinity to macromolecules. J. Am. Chem. Soc. 120, 10258-10259 (1998).
13. Chen, A., & Shapiro, M. J. NOE pumping. 2. A high-throughput method to determine compounds with binding affinity to macromolecules by NMR. J. Am. Chem. Soc. 122, 414-415 (2000).
14. Dalvit, C. et al. Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water. J. Biomol. NMP 18, 65-68 (2000).
15. Gibbs, S. J. & Johnson, C. S. A PFG-NMR experiment for accurate diffusion and flow studies in the presence of Eddy currents. J. Magn. Reson. 93, 395-402 (1991).
16. Altieri, A. S., Hinton, D. P. & Byrd, R. A. Association of biomolecular systems via pulse-field gradient NMR self-diffusion measurements. J. Am. Chem. Soc. 117, 7566-7567 (1995).
17. Shuker, S. B., Hajduk, P. J., Meadows, R. P. & Fesik, S. W. Discovering high-affinity ligands for proteins: SAR by NMR. Science 274, 1531-1534 (1996).
18. Hajduk, P. J. et al. NMR-based discovery of lead inhibitors that block DNA-binding of the human papillomavirus protein E2 protein. J. Med. Chem. 40, 3144-3150 (1997).
19. Hajduk, P. J. et al. Discovery of potent non-peptide inhibitors of stromelysin using SAR by NMR. J. Am. Chem. Soc. 119, 5818-5827 (1997).
20. Hajduk, P. J. et al. Novel inhibitors of Erm methyltransferases from NMR and parallel synthesis. J. Med. Chem. 42, 3852-3859 (1999).
21. Boehm, H. J. et al. Novel inhibitors of DNA girase: 3D structure based biased needle screening, hit validation by biophysical methods and 3D guided optimization. A promising alternative to random screening. J. Med. Chem. 43, 2664-2674 (2000).
22. Ross, A. & Senn, H. Automation of measurements and data evaluation in biomolecular NMIR screening. Drug Discov. Today 6, 583-593 (2001).
23. Hajduk, P. J. et al. High-throughput nuclear magnetic resonance-based screening. J. Med. Chem. 42, 2315-2317(1999).
24. Fejzo, J. et al. The SHAPES strategy: an NMR-based approach for lead generation in drug discovery. Chem. Biol. 6, 755-769 (1999).
25. Bemis, G. W. & Murcko, M. A. The properties of known drugs. 1. Molecular frameworks J. Med. Chem. 39, 2887-2893 (1996).
26. 13C-labeled methyl groups, J. Am. Chem. Soc. 122, 7898-7904 (2000).
27. Wüthrich, K. NMR in Structural Biology (World Scientific, Singapore, 1995).
28. Li, D. W., DeRose, E. F. & London, R. E. The inter-ligand Overhauser effect: a powerful new NMR approach for mapping structural relationships of macromolecular ligands. J. Biomol. NMR 15, 71-76 (1999).
29. London, R. E. Theoretical analysis of the inter-ligand Overhauser effect: a new approach for mapping structural relationships of macromolecular ligands. J. Magn. Reson. 141, 301-311 (1999).
30. Jahnke, W. et al. Second-site NMR screening with a spin-labeled first ligand. J. Am. Chem. Soc. 122, 7394-7395 (2000).
31. Meinecke, R. & Meyer, B. Determination of the binding specificity of an integral membrane protein by saturation transfer difference NMR: RGD peptide ligands binding to integrin llb3. J. Med. Chem. 44, 3059-3065 (2001).
32. Fernández, C. et al. Solution NMR studies of the integral membrane proteins OmpX and OmpA from Escherichia coli. FEBS Lett. 504, 173-178 (2001).
33. Serber, Z., Ledwidge, R., Miller, S. M. & Dötsch, V. Evaluation of parameters critical to observing proteins inside living Escherichia coli by in-cell NMR spectroscopy. J. Am. Chem. Soc. 123, 8895-8901 (2001).
34. Bloch, F. Nuclear induction. Phys. Rev. 70, 460-474 (1946).
35. Purcell, E. M., Torrey, E. C. & Pound, R. V. Resonance absorption by nuclear magnetic moments in a solid. Phys. Rev. 69, 37-38 (1946).
36. The Protein Data Bank. Nucleic Acids Res. 28, 235-242 (2000).
37. Structural genomics. Nature Struct. Biol. 7 (Suppl.) (2000).
38. 15N nuclear magnetic resonance. Methods Enzymol. 177, 44-73 (1989).
39. Kay, L. E. & Gardner, K. H. Solution NMR spectroscopy beyond 25 kDa. Curr. Opin. Struct. Biol. 7, 722-731 (1997).
40. Kay, L. E., Ikura, M., Tschudin, R. & Bax, A. Three-dimensional triple-resonance NMR-spectroscopy of isotopically enriched proteins. J. Magn. Reson. 89, 496-514 (1990).
41. Xu, R., Ayers, B., Cowburn, D. & Muir, T. W. Chemical ligation of folded recombinant proteins: segmental isotopic labeling of domains for NMR studies. Proc. Natl Acad. Sci. USA 96, 388-393 (1999).
42. 2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. Proc. Natl Acad. Sci. USA 94, 12366-12371 (1997).
43. Wüthrich, K. The second decade - into the third millennium. Nature Struct. Biol. 5, 492-495 (1998).
44. 13C-labeled proteins. J. Am. Chem. Soc. 120, 6394-6400 (1998).
45. Salzmann, M., Pervushin, K., Wider, G., Senn, H. & Wüthrich, K. NMR assignment and secondary structure determination of an octameric 110 kDa protein using TROSY in triple resonance experiments. J. Am. Chem. Soc. 122, 7543-7548 (2000).
46. Pellecchia, M., Sebbel, P., Hermanns, U., Glockshuber, R. & Wüthrich, K. Pilus chaperone FimC-adhesin FimH interactions mapped by TROSY-NMR. Nature Struct. Biol. 6, 336-339 (1999).
47. Pellecchia, M. et al. SEA-TROSY (solvent exposed amides with TROSY): a method to resolve the problem of spectral overlap in very large proteins. J. Am. Chem. Soc. 123, 4633-4634 (2001).