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Overview of NMR in Drug Design

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Modern Magnetic Resonance

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Abstract

NMR spectroscopy is an extremely valuable tool in the pharmaceutical sciences. This chapter gives an overview of the use of this tool in drug design. It sets the scene for the specialist chapters that are included in this Handbook of Modern Magnetic Resonance.

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Abbreviations

COSY:

Correlation spectroscopy

Da:

Dalton

FBS:

Fragment-based screening

HMBC:

Heteronuclear multiple-bond correlation

HMQC:

Heteronuclear multiple quantum coherence

HSQC:

Heteronuclear single quantum coherence

HTS:

High-throughput screening

MHz:

Megahertz

MS:

Mass spectrometry

NOE:

Nuclear Overhauser effect

NOESY:

Nuclear Overhauser effect spectroscopy

SPR:

Surface plasmon resonance

STD:

Saturation transfer difference spectroscopy

TROSY:

Transverse relaxation-optimized spectroscopy

WaterLOGSY:

Water-ligand observed gradient spectroscopy

References

  1. Erlanson DA, Fesik SW, Hubbard RE, Jahnke W, Jhoti H. Twenty years on: the impact of fragments on drug discovery. Nat Rev Drug Discov. 2016;15:605–19.

    Article  Google Scholar 

  2. Gossert AD, Jahnke W. NMR in drug discovery: a practical guide to identification and validation of ligands interacting with biological macromolecules. Prog Nucl Magn Reson Spectrosc. 2016;97:82–125.

    Article  Google Scholar 

  3. Aldrich C, Bertozzi C, Georg GI, Kiessling L, Lindsley C, Liotta D, et al. The ecstasy and agony of assay interference compounds. ACS Cent Sci. 2017;3:143–7.

    Article  Google Scholar 

  4. Renaud JP, Chung CW, Danielson UH, Egner U, Hennig M, Hubbard RE, et al. Biophysics in drug discovery: impact, challenges and opportunities. Nat Rev Drug Discov. 2016;15:679–98.

    Article  Google Scholar 

  5. Schirra JH, Craik DJ. Overview of NMR in the pharmaceutical sciences. In: Webb GA, editor. Modern magnetic resonance. 2 Dordrecht: Springer; 2006. p. 1177–84.

    Google Scholar 

  6. Everett JR. Drug discovery and development: the role of NMR. eMagRes. 2015;4:137–50.

    Article  Google Scholar 

  7. Dias DM, Ciulli A. NMR approaches in structure-based lead discovery: recent developments and new frontiers for targeting multi-protein complexes. Prog Biophys Mol Biol. 2014;116:101–12.

    Article  Google Scholar 

  8. Shuker SB, Hajduk PJ, Meadows RP, Fesik SW. Discovering high-affinity ligands for proteins: SAR by NMR. Science. 1996;274:1531–4.

    Article  Google Scholar 

  9. Burke JP, Bian ZG, Shaw S, Zhao B, Goodwin CM, Belmar J, et al. Discovery of tricyclic indoles that potently inhibit Mcl-1 using fragment-based methods and structure-based design. J Med Chem. 2015;58:3794–805.

    Article  Google Scholar 

  10. Elipe MVS, Milburn RR. Monitoring chemical reactions by low-field benchtop NMR at 45MHz: pros and cons. Magn Reson Chem. 2016;54:437–43.

    Article  Google Scholar 

  11. Gomez MV, de la Hoz A. NMR reaction monitoring in flow synthesis. Beilstein J Org Chem. 2017;13:285–300.

    Article  Google Scholar 

  12. Ahmed-Omer B, Sliwinski E, Cerroti JP, Ley SV. Continuous processing and efficient in situ reaction monitoring of a hypervalent iodine(III) mediated cyclopropanation using benchtop NMR spectroscopy. Org Process Res Dev. 2016;20:1603–14.

    Article  Google Scholar 

  13. Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov. 2005;4:206–20.

    Article  Google Scholar 

  14. Breton RC, Reynolds WF. Using NMR to identify and characterize natural products. Nat Prod Rep. 2013;30:501–24.

    Article  Google Scholar 

  15. Gaudencio SP, Pereira F. Dereplication: racing to speed up the natural products discovery process. Nat Prod Rep. 2015;32:779–810.

    Article  Google Scholar 

  16. Pauli GF, Chen SN, Lankin DC, Bisson J, Case RJ, Chadwick LR, et al. Essential parameters for structural analysis and dereplication by H-1 NMR spectroscopy. J Nat Prod. 2014;77:1473–87.

    Article  Google Scholar 

  17. Lisi GP, Loria JP. Solution NMR spectroscopy for the study of enzyme allostery. Chem Rev. 2016;116:6323.

    Article  Google Scholar 

  18. Chen L, Wilder PT, Drennen B, Tran J, Roth BM, Chesko K, et al. Structure-based design of 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines as inhibitors of myeloid cell leukemia-1 (Mcl-1). Org Biomol Chem. 2016;14:5505–10.

    Article  Google Scholar 

  19. Venters RA, Thompson R, Cavanagh J. Current approaches for the study of large proteins by NMR. J Mol Struct. 2002;602:275–92.

    Article  Google Scholar 

  20. Ruschak AM, Kay LE. Methyl groups as probes of supra-molecular structure, dynamics and function. J Biomol NMR. 2010;46:75–87.

    Article  Google Scholar 

  21. Grzesiek S, Anglister J, Ren H, Bax A. C-13 line narrowing by H-2 decoupling in H-2/C-13/N-15-enriched proteins – application to triple-resonance 4D J-connectivity of sequential amides. J Am Chem Soc. 1993;115:4369–70.

    Article  Google Scholar 

  22. Orts J, Walti MA, Marsh M, Vera L, Gossert AD, Guntert P, et al. NMR-based determination of the 3D structure of the ligand-protein interaction site without protein resonance assignment. J Am Chem Soc. 2016;138:4393–400.

    Article  Google Scholar 

  23. Hajduk PJ, Mack JC, Olejniczak ET, Park C, Dandliker PJ, Beutel BA. SOS-NMR: a saturation transfer NMR-based method for determining the structures of protein-ligand complexes. J Am Chem Soc. 2004;126:2390–8.

    Article  Google Scholar 

  24. Guan JY, Keizers PHJ, Liu WM, Lohr F, Skinner SP, Heeneman EA, et al. Small-molecule binding sites on proteins established by paramagnetic NMR spectroscopy. J Am Chem Soc. 2013;135:5859–68.

    Article  Google Scholar 

  25. Emwas AHM, Salek RM, Griffin JL, Merzaban J. NMR-based metabolomics in human disease diagnosis: applications, limitations, and recommendations. Metabolomics. 2013;9:1048–72.

    Article  Google Scholar 

  26. Nicholson JK, Oflynn MP, Sadler PJ, Macleod AF, Juul SM, Sonksen PH. Proton-nuclear-magnetic-resonance studies of serum, plasma and urine from fasting normal and diabetic subjects. Biochem J. 1984;217:365–75.

    Article  Google Scholar 

  27. Reily MD, Tymiak AA. Metabolomics in the pharmaceutical industry. Drug Discov Today Technol. 2015;13:25.

    Article  Google Scholar 

  28. Gonzalez FJ, Fang ZZ, Ma XC. Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity. Expert Opin Drug Metab Toxicol. 2015;11:869–81.

    Article  Google Scholar 

  29. Beyoglu D, Idle JR. Metabolomics and its potential in drug development. Biochem Pharmacol. 2013;85:12–20.

    Article  Google Scholar 

  30. Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC. Metabolic phenotyping in clinical and surgical environments. Nature. 2012;491:384–92.

    Article  Google Scholar 

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Authors and Affiliations

  1. Institute for Molecular Bioscience, The University of Queensland, 4072, Brisbane, QLD, Australia

    David J Craik & Hayden Peacock

Authors
  1. David J Craik
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  2. Hayden Peacock
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Corresponding author

Correspondence to David J Craik .

Editor information

Editors and Affiliations

  1. Royal Society of Chemistry, London, United Kingdom

    Graham A. Webb

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© 2017 Springer International Publishing AG

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Craik, D.J., Peacock, H. (2017). Overview of NMR in Drug Design. In: Webb, G. (eds) Modern Magnetic Resonance. Springer, Cham. https://doi.org/10.1007/978-3-319-28275-6_112-1

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  • DOI: https://doi.org/10.1007/978-3-319-28275-6_112-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-28275-6

  • Online ISBN: 978-3-319-28275-6

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

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