Journal of the Korean Magnetic Resonance Society (한국자기공명학회논문지)

Korean Magnetic Resonance Society (한국자기공명학회)
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NMR methods in fragment based drug discovery

  • Lim, Jongsoo (Molecular Pharmacology Team, Innovative Medicine Research Laboratories, Dong-a Socio Holdings)
  • Received : 2015.08.06
  • Accepted : 2015.11.25
  • Published : 2015.12.20
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Abstract

Nuclear magnetic resonance (NMR) spectroscopy, owing to its ability to provide atomic level information on molecular structure, dynamics and interaction, has become one of the most powerful methods in early drug discovery where hit finding and hit-to-lead generation are mainly pursued. In recent years, drug discovery programs originating from the fragment-based drug discovery (FBDD) strategies have been widely incorporated into academia and industry in which a wide variety of NMR methods become an indispensable arsenal to elucidate the binding of small molecules onto bimolecular targets. In this review, I briefly describe FBDD and introduce NMR methods mainly used in FBDD campaigns of my company. In addition, quality control of fragment library and practical NMR methods in industrial aspect are discussed shortly.

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References

  1. R. Macarron, M. N. Banks, D. Bojanic, D. J. Burns, D. A. Cirovic, T. Garyantes, D. V. Green, R. P. Hertzberg, W. P. Janzen, J. W. Paslay, U. Schopfer, and G. S. Sittampalam, Nat. Rev. Drug Discov. 10, 3 (2011) https://doi.org/10.1038/nrd3348
  2. S. B. Shuker, P. J. Hajduk, R. P. Meadows, and S. W. Fesik, Science 274, 5292 (1996)
  3. W. P. Jencks, Proc. Natl. Acad. Sci. U S A. 78, 7 (1981)
  4. C. A. Lipinski, F. Lombardo, B. W. Dominy, and P. J. Feeney, Adv. Drug. Deliv. Rev. 46, 1-3 (2001) https://doi.org/10.1016/S0169-409X(00)00145-9
  5. T. sMaurer, L. S. Garrenton, A. Oh, K. Pitts, D. J. Anderson, N. J. Skelton, B. P. Fauber, B. Pan, S. Malek, D. Stokoe, M. J. Ludlam, K. K. Bowman, J. Wu, A. M. Giannetti, M. A. Starovasnik, I. Mellman, P. K. Jackson, J. Rudolph, W. Wang, and G. Fang, Proc. Natl. Acad. Sci. U S A. 109, 14 (2012)
  6. Q. Sun, J. P. Burke, J. Phan, M. C. Burns, E. T. Olejniczak, A. G. Waterson, T. Lee, O. W. Rossanese, and S. W. Fesik, Angew. Chem. Int. Ed. Engl. 51, 25 (2012)
  7. H. Chen, X. Zhou, A. Wang, Y. Zheng, Y. Gao, and J. Zhou, Drug Discov. Today 20, 1 (2015)
  8. M. Pellecchia, D. S. Sem, and K. Wuthrich, Nat. Rev. Drug Discov. 1, 3 (2002) https://doi.org/10.1038/nrd713
  9. M. Mayer and B. Meyer, Angewandte Chemie International Edition 38, 12 (1999)
  10. C. Dalvit, P. Pevarello, M. Tato, M. Veronesi, A. Vulpetti, and M. Sundstrom, J.Biomol.NMR 18, 1 (2000) https://doi.org/10.1023/A:1008379605403
  11. J. B. Jordan, L. Poppe, X. Xia, A. C. Cheng, Y. Sun, K. Michelsen, H. Eastwood, P. D. Schnier, and T. Nixey, W. Zhong, J.Med.Chem. 55, 2 (2012) https://doi.org/10.1021/jm200607g
  12. C. Dalvit, M. Flocco, M. Veronesi, and B. J. Stockman, Comb.Chem.High Throughput Screen 5, 8 (2002)
  13. L. Oster, S. Tapani, Y. Xue, and H. Kack, Drug Discov.Today 20, 9 (2015)
  14. C. Aguirre, T. t. Brink, J.-F. Guichou, O. Cala, and I. Krimm, PLoS One 9, 7 (2014)
  15. M. Mayer and B. Meyer, Journal of the American Chemical Society 123, 25 (2001)
  16. J. Baell and M. A. Walters, Nature 513, 7519 (2014)
  17. S. R. Laplante, R. J. Carson, J. R. Gillard, N. Aubry, R. Coulombe, S. Bordeleau, P. R. Bonneau, M. Little, J. A. Omeara, and P. L. Beaulieu, J. Med. Chem. (2013)
  18. D. M. Dias and A. Ciulli, Prog. Biophys. Mol. Biol. 116, 2-3 (2014)
  19. J. Y. Guan, P. H. Keizers, W. M. Liu, F. Lohr, S. P. Skinner, E. A. Heeneman, H. Schwalbe, M. Ubbink, and G. Siegal, J. Am. Chem. Soc. 135, 15 (2013)
  20. C. Aguirre, T. ten Brink, O. Walker, F. Guilliere, D. Davesne, and I. Krimm, PLoS One 8, 5 (2013)