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Can Enzyme Mimics Compete with Catalytic Antibodies?

  • Christopher J. Walter
  • Lindsey G. Mackay
  • Jeremy K. M. Sanders
Part of the NATO ASI Series book series (NSSE, volume 320)

Abstract

Many scientists are trying to create synthetic host molecules which mimic some of the recognition and catalytic properties of real enzymes. Enzymes catalyse chemical reactions with an efficiency that is awe-inspiring: they can bring together two unreactive substrate molecules, induce them to react, and then release the product at an astonishing speed. They are also subtle, usually forming just one of the many products that would result from a simple reaction carried out by a chemist. We know in general terms that enzymes achieve their catalysis by binding two substrate molecules in close proximity, by using binding energy and conformational changes to facilitate the approach to the transition state, and by using their own functional groups to intervene chemically, but we do not know all the rules. In particular we do not understand the balance between structural rigidity leading to pre-organised binding sites, and flexibility which allows the site to recognise and respond to the shape and size of the bound substrate.

Keywords

Cholic Acid Catalytic Antibody Tetrahedral Intermediate Free Energy Profile Acyl Transfer Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Kirby, A. J. (1994)Angew. Chemie Intl. Edn., 33, 551–553.CrossRefGoogle Scholar
  2. 2.
    Johnsson, K., Alleman, R. K., Widmer, H., and Benner, S. A. (1993)Nature, 365, 530–533.CrossRefGoogle Scholar
  3. 3.
    Breslow, R (1991) Acc. Chem. Res., 24, 318–324.Google Scholar
  4. 4.
    Bonar-Law, R. P., Mackay, L. G, Walter, C. J., Marvaud, V., and Sanders, J. K. M. (1994)Pure Appl Chem., 66, 803–810.CrossRefGoogle Scholar
  5. 5.
    Bonar-Law, R.P. and Davis, A. P. (1993) Tetrahedron, 49, 9829–9854; Bonar-Law, R.P. and Sanders, J. K. M. (1991) J. Chem. Soc. Chem. Commun., 574–577.Google Scholar
  6. 6. (a)
    Diederich, F. and Lutter, H.-D.(1989)J. Amer. Chem. Soc., 111, 8438–8446;CrossRefGoogle Scholar
  7. 6. (b)
    Mock, W. L., Irra, T. A., Wepsiec, J. P., and Adhya, M. (1989) J. Org. Chem., 54, 5302–5308;CrossRefGoogle Scholar
  8. 6. (c)
    Kelly, T. R., Bridger, G. J., and Zhao, C. (1990) J. Amer. Chem. Soc, 112, 8024–8034;CrossRefGoogle Scholar
  9. 6. (d)
    Nowick, J. S., Feng, Q., Tjivikua, T., Ballester, P., and Rebek, J. Jr (1991) J. Amer. Chem. Soc, 113, 8831–8839;CrossRefGoogle Scholar
  10. 6. (e)
    Schneider, H.-J., Kramer, R. and Rammo, J. (1993) J. Amer. Chem. Soc, 115, 8980–8984.CrossRefGoogle Scholar
  11. 7.
    For reviews see the special issue of Accounts of Chemical Research, August 1993.Google Scholar
  12. 8. (a)
    Benner, S.(1993)Science, 261, 1402–1404CrossRefGoogle Scholar
  13. 8. (b)
    Bartel, D. P. and Szostak, J. W. (1993) Science, 261, 1411–1418.CrossRefGoogle Scholar
  14. 9.
    Flam, F. (1994) Science, 263, 1221–1222;Heilmann, J. and Maier, W. F. (1994) Angew. Chemie Intl. Edn.,33, 471–473.Google Scholar
  15. 10.
    Walter, C. J. and Sanders, J. K. M.(1995)Angew. Chemie Intl. Edn., 34, 217–219.CrossRefGoogle Scholar
  16. 11.
    Walter, C. J., Anderson, H. L., and Sanders, J. K. M. (1993) J. C. S., Chem. Commun., 458–460.Google Scholar
  17. 12.
    Kirby, A. J. (1980) Adv. Phys. Org. Chem., 17, 183–278.CrossRefGoogle Scholar
  18. 13.
    Anderson, H. L., Bashall, A., Henrick, K., McPartlin, M., and Sanders, J. K. M.(1994)Angew. Chemie Intl. Edn. Engl, 33, 429–431.CrossRefGoogle Scholar
  19. 14.
    Mackay, L. G., Bonar-Law, R. P., and Sanders, J. K. M. (1992) J.C.S., Chem. Commun., 43–44.Google Scholar
  20. 15.
    Anderson, S., Anderson, H. L., and Sanders, J. K. M.(1993)Accounts of Chemical Research, 26, 469–475.CrossRefGoogle Scholar
  21. 16.
    Mackay, L. G., Wylie, R. S., and Sanders, J. K. M. (1994) J. Amer. Chem. Soc, 116, 3141–3142.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Christopher J. Walter
    • 1
  • Lindsey G. Mackay
    • 1
  • Jeremy K. M. Sanders
    • 1
  1. 1.Cambridge Centre for Molecular RecognitionUniversity Chemical LaboratoryCambridgeUK

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