Skip to main content
SpringerLink
Log in

Studying Noncovalent Small Molecule Interactions with Protein and RNA Targets by Mass Spectrometry

  • Chapter
Mass Spectrometry in Biology & Medicine

Abstract

Developing methods for elucidating the mechanism of action of drugs and inhibitors on a structural level is an active area of biomedical and pharmaceutical research. To develop new therapies at an increasing pace, more new drugs need to be synthesized or discovered, more novel macromolecular targets need to be identified, and compounds need to be characterized, screened and evaluated at a faster rate. Advances and application of combinatorial chemistry address the need for more compounds [1, 2], whereas research endeavors such as genomics [3] and proteomics [4, 5] have shown great potential for uncovering novel targets. Methods for high-throughput screening using a variety of large-scale automated processes and robotics have been developed to further address some of these important needs [6]. However, biophysical techniques are still needed to fully elucidate the fundamental aspects of inhibitor action on its target.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. A Practical Guide to Combinatorial Chemistry,A. W. Czarnik and S. H. DeWitt, Eds.; American Chemical Society: Washington, DC, 1997.

    Google Scholar 

  2. A. W. Czarnik, Anal. Chem. 1998, 70, 378A - 386A.

    Article  Google Scholar 

  3. J. Lillie, Drug Dey. Res. 1997, 41, 160–172.

    Article  Google Scholar 

  4. A. Shevchenko, O. N. Jensen, A. V. Podtelejnikov, F. Sagliocco, M. Wilm, O. Vorm, P. Mortensen, A. Shevchenko, H. Boucherie and M. Mann, Proc. Natl. Acad. Sci. USA 1996, 93, 14440–14445.

    Article  Google Scholar 

  5. P. Roepstorff, Curr. Opin. Biotechnol. 1997, 8, 6–13.

    Article  Google Scholar 

  6. L. Silverman, R. Campbell and J. R. Broach, Curr. Opin. Chem. Biol. 1998, 2, 397–403.

    Article  Google Scholar 

  7. J. A. Loo, Bioconjugate Chem. 1995, 6, 644–665.

    Article  Google Scholar 

  8. J. B. Fenn, M. Mann, C. K. Meng, S. F. Wong and C. M. Whitehouse, Science 1989, 246, 64–71.

    Article  CAS  Google Scholar 

  9. F. S. Pullen, G. L. Perkins, K. I. Burton, R. S. Ware, M. S. Teague and J. P. Kiplinger, J. Am. Soc. Mass Spectrom. 1995, 6, 394–399.

    Article  CAS  Google Scholar 

  10. L. C. E. Taylor, R. L. Johnson and R. Raso, J. Am. Soc. Mass Spectrom. 1995, 6, 387–393.

    Article  CAS  Google Scholar 

  11. R. C. Spreen and L. M. Schaffter, Anal. Chem. 1996, 68, 414A - 419A.

    Article  CAS  Google Scholar 

  12. S. Kaur, L. McGuire, D. Tang, G. Dollinger and V. Huebner, J. Protein Chem. 1997, 16, 505–511.

    Article  CAS  Google Scholar 

  13. M. A. Kelly, H. Liang, I.-I. Sytwu, I. Vlattas, N. L. Lyons, B. R. Bowen and L. P. Wennogle, Biochemistry 1996, 35, 11747–11755.

    CAS  Google Scholar 

  14. Y. F. Hsieh, N. Gordon, F. Regnier, N. Afeyan, S. A. Martin and G. J. Vella, Mol. Diversity 1997, 2, 189–196.

    Article  CAS  Google Scholar 

  15. R. B. van Breemen, C.-R. Huang, D. Nikolic, C. P. Woodbury, Y.-Z. Zhao and D. L. Venton, Anal. Chem. 1997, 69, 2159–2164.

    Article  Google Scholar 

  16. J. A. Loo, Eur. Mass Spectrom. 1997, 3, 93–104.

    Article  Google Scholar 

  17. R. Wieboldt, J. Zweigenbaum and J. Henion, Anal. Chem. 1997, 69, 1683–1691.

    Article  CAS  Google Scholar 

  18. M. M. Siegel, K. Tabei, G. A. Bebernitz and E. Z. Baum, J. Mass Spectrom. 1998, 33, 264–273.

    Article  CAS  Google Scholar 

  19. J. A. Loo, Mass Spectrom. Rev. 1997, 16, 1–23.

    Article  Google Scholar 

  20. J. A. Loo, K. A. Sannes-Lowery, P. Hu, D. P. Mack and H.-Y. Mei, in New Methods for the Study of Biomolecular Complexes, W. Ens, K. G. Standing, and I. V. Chernushevich, Eds.; Kluwer: Dordrecht, Netherlands, 1998; pp 83–99.

    Google Scholar 

  21. J. A. Loo, P. Hu, P. McConnell, W. T. Mueller, T. K. Sawyer and V. Thanabal, J. Am. Soc. Mass Spectrom. 1997, 8, 234–243.

    Article  CAS  Google Scholar 

  22. K. A. Sannes-Lowery, P. Hu, D. P. Mack, H.-Y. Mei and J. A. Loo, Anal. Chem. 1997, 69, 5130–5135.

    Article  CAS  Google Scholar 

  23. J. A. Loo and K. A. Sannes-Lowery, in Mass Spectrometry of Biological Materials (2nd Ed.), B. S. Larsen and C. N. McEwen, Eds.; Dekker: New York, 1998; pp 345–367.

    Google Scholar 

  24. A. Wlodawer, M. Miller, M. Jaskolski, B. K. Sathyanarayana, E. Baldwin, I. T. Weber, L. M. Selk, L. Clawson, J. Schneider and S. B. H. Kent, Science 1989, 245, 616–621.

    Article  CAS  Google Scholar 

  25. M. Baca and S. B. H. Kent, J. Am. Chem. Soc. 1992, 114, 3992–3993.

    Article  CAS  Google Scholar 

  26. P. M. D. Fitzgerald, B. M. McKeever, J. F. VanMiddlesworth, J. P. Springer, J. C. Heimbach, C.-T. Leu, W. K. Herber, R. A. F. Dixon and P. L. Darke, J. Biol. Chem. 1990, 265, 14209–14219.

    CAS  Google Scholar 

  27. P. L. Darke, S. P. Jordan, D. L. Hall, J. A. Zugay, J. A. Shafer and L. C. Kuo, Biochemistry 1994, 33, 98–105.

    Article  CAS  Google Scholar 

  28. Q.-Z. Ye, L. L. Johnson, D. J. Hupe and V. Baragi, Biochemistry 1992, 31, 11231–11235.

    Article  CAS  Google Scholar 

  29. P. R. Gooley, J. F. O’Connell, A. I. Marcy, G. C. Cuca, S. P. Salowe, B. L. Bush, J. D. Hermes, C. K. Esser, W. K. Hagmann, J P. Springer and B. A. Johnson, Nature Struct. Biol. 1994, 1, 111–118.

    Article  CAS  Google Scholar 

  30. J. W. Becker, A. I. Marcy, L. L. Rokosz, M. G. Axel, J. J. Burbaum, P. M. D. Fitzgerald, P. M. Cameron, C. K. Esser, W. K. Hagmann, J. D. Hermes and J. P. Springer, Protein Sci. 1995, 4, 1966–1976.

    Article  CAS  Google Scholar 

  31. S. R. Van Doren, A. V. Kurochkin, W. Hu, Q.-Z. Ye, L. L. Johnson, D. J. Hupe and E. R. P. Zuiderweg, Protein Sci. 1995, 4, 2487–2498.

    Article  Google Scholar 

  32. V. Dhanaraj, Q.-Z. Ye, L. L. Johnson, D. J. Hupe, D. F. Ortwine, J. B. Dunbar, Jr., J. R. Rubin, A. Pavlovsky, C. Humblet and T. L. Blundell, Structure (London) 1996, 4, 375–386.

    Article  CAS  Google Scholar 

  33. P. Hu, Q.-Z. Ye and J. A. Loo, Anal. Chem. 1994, 66, 4190–4194.

    Article  CAS  Google Scholar 

  34. R. Feng, A. L. Castelhano, R. Billedeau and Z. Yuan, J. Am. Soc. Mass Spectrom. 1995, 6, 1105–1111.

    Article  CAS  Google Scholar 

  35. D.Grobelny, L. Poncz and R. E. Galardy, Biochemistry 1992, 31,7152–7154.

    Google Scholar 

  36. H.-Y. Mei, D. P. Mack, A. A. Galan, N. S. Halim, A. Heldsinger, J. A. Loo, D. W. Moreland, K. A. Sannes-Lowery, L. Sharmeen, H. N. Truong and A. W. Czarnik, Bioorg. Med. Chem. 1997, 5, 1173–1184.

    Article  CAS  Google Scholar 

  37. H.-Y. Mei, A. A. Galan, N. S. Halim, D. P. Mack, D. W. Moreland, K. B. Sanders, H. N. Truong and A. W. Czarnik, Bioorg. Med. Chem. Lett. 1995, 5, 2755–2760.

    Article  CAS  Google Scholar 

  38. S. Wang, P. W. Huber, M. Cui, A. W. Czarnik and H.-Y. Mei, Biochem- istry 1998, 37, 5549–5557.

    Google Scholar 

  39. H.-Y. Mei, M. Cui, A. Heldsinger, S. M. Lemrow, J. A. Loo, K. A. Sannes- Lowery, L. Sharmeen and A. W. Czarnik, Biochemistry,in press.

    Google Scholar 

  40. H. Wang and Y. Tor, J. Am. Chem. Soc. 1997, 119, 8734–8735.

    Article  CAS  Google Scholar 

  41. X. Cheng, R. D. Chen, J. E. Bruce, B. L. Schwartz, G. A. Anderson, S. A. Hofstadler, D. C. Gale, R. D. Smith, J. M. Gao, G. B. Sigal, M. Mammen and G. M. Whitesides, J. Am. Chem. Soc. 1995, 117, 8859–8860.

    Article  CAS  Google Scholar 

  42. C. V. Robinson, E. W. Chung, B. B. Kragelund, J. Knudsen, R. T. Aplin, F. M. Poulsen and C. M. Dobson, J. Am. Chem. Soc. 1996, 118,86468653.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemistry Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Joseph A. Loo, Venkataraman Thanabal & Houng-Yau Mei

Authors
  1. Joseph A. Loo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Venkataraman Thanabal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Houng-Yau Mei
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California, San Francisco, CA, USA

    A. L. Burlingame  & Michael A. Baldwin  & 

  2. SmithKline Beecham Pharmaceuticals, King of Prussia, PA, USA

    Steven A. Carr

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Loo, J.A., Thanabal, V., Mei, HY. (2000). Studying Noncovalent Small Molecule Interactions with Protein and RNA Targets by Mass Spectrometry. In: Burlingame, A.L., Carr, S.A., Baldwin, M.A. (eds) Mass Spectrometry in Biology & Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-719-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-719-2_5

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9829-5

  • Online ISBN: 978-1-59259-719-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation