Theory of Radioimmunoassays and Hormone-Receptor Interactions:

II. Simulation of Antibody Divalency, Cooperativity and Allosteric Effects
  • D. Rodbard
  • R. E. Bertino
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 36)


Since antibody and some hormone receptor molecules are known to possess two binding sites, it is possible that the intrinsic affinity constant for the “second site”, after one site is filled, is greater than the intrinsic affinity constant for the first site; this would result in “cooperative” or apparent “allosteric” effects. The mathematical theory of “cooperative” binding systems, both at equilibrium and in the transient state, has been applied to radioimmunoassay systems. The effects of affinity constants, antibody concentration, and “tracer” concentration, have been examined in several coordinate systems. Further, the kinetics of these reaction systems have been simulated. This theory should be useful in design and analysis of experiments to test for the presence of “cooperativity” effects.


Dose Response Curve Antibody Concentration Affinity Constant Scatchard Plot Cooperativity Effect 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Matsukura, S., West, C.D., Ichikawa, Y., Jubiz, W., Harada, G., and Tyler, F.H., J. Lab. Clin. Med. 77: 490, 1971.PubMedGoogle Scholar
  2. 2.
    Odell, W.D., and W.H. Daughaday, Principles of Competitive Protein Binding Assays: Lippincott, Phila., 1971, (see Miles, p. 24, and Korenman, Rodbard, p. 20l).Google Scholar
  3. 3.
    Goodfriend, T., in: Margoulies, M., and Greenwood, F. (eds.), Protein and Polypeptide Hormones, Excerpta Medica, Amsterdam, 1972, in press.Google Scholar
  4. 4a.
    Weintraub, B.D., Kadesky, Y.M., Rosen, S.W., Clin. Res., 20: 444, 1972.Google Scholar
  5. Weintraub, B.D., Rosen, S.W., Mc-Cammon, J.A., Perlman, R.L., Endocrinology (submitted).Google Scholar
  6. 5.
    Ellis, D.J., and Ringold, H.J., in McKerns, K.W. (ed.), The Sex Steroids — Molecular Mechanisms, Appleton Century Crafts, New York, pp. 73–106, 1971.Google Scholar
  7. 6.
    Monod, J., Changeux, J-P, Jacob, F., J. Mol. Biol., 6: 306, 1963.PubMedCrossRefGoogle Scholar
  8. 7.
    Monod, J., Wyman, J., Changeux, J-P, J. Mol. Biol., 12: 88, 1965.PubMedCrossRefGoogle Scholar
  9. 8.
    Edsall, J.T., Wyman, J., Biophysical Chemistry, Academic Press, N.Y., 1: 613, 1958.Google Scholar
  10. 9.
    Koshland, D.E., Nemethy, G., Filmer, D., Biochemistry, 5.: 365, 1966.PubMedCrossRefGoogle Scholar
  11. 10.
    Fletcher, J.E., Spector, A.A., Ashbrook, J.D., Biochemistry, 9: 4580, 1970.PubMedCrossRefGoogle Scholar
  12. 11.
    Gibson, Q.H., J. Biol. Chem., 245:, 3285, 1970.Google Scholar
  13. 12.
    Sweeny, J.R., Fisher, J.R., Biochemistry 7: 56l, 1968.CrossRefGoogle Scholar
  14. 13.
    Kirschner, K., Gallego, E., Schuster, I., J. Mol. Biol., 58: 29, 1971.PubMedCrossRefGoogle Scholar
  15. 14.
    Chun, P.W., Biophysical J., 10: 577, 1970.CrossRefGoogle Scholar
  16. 15.
    Ling, G.N., Proc. Nat. Academy Sci. U.S.67 296, 1970.CrossRefGoogle Scholar
  17. 16.
    Ho, C., Baldassare, J.J., Charache, S., Proc. Nat. Acad. Sci., U.S.66 722, 1970.PubMedCrossRefGoogle Scholar
  18. 17.
    Schwartz, G., Eur. J. Biochem., 12: 442 ,1970.Google Scholar
  19. 18.
    Berson, S.A., and Yalow, R.S., J. Clin. Invest., 38: 1996, 1959.PubMedCrossRefGoogle Scholar
  20. 19.
    Feldman, H., Rodbard, D., and Levine, D., Anal. Biochem., 45: 530, 1972.PubMedCrossRefGoogle Scholar
  21. 20.
    Rodbard, D., Weiss, G.H., Analytical Biochemistry (in press).Google Scholar
  22. 21.
    Feldman, H., and Rodbard, D., in Odell, W.D. and Daughaday, W.H., Principles of Competitive Protein Binding Assays, Lippincott, Phila., p. 158, 1971.Google Scholar
  23. 22.
    Knott, G.D., Reece, D.K., Proceedings On-Line 72 Symposium, Brunei Univ., Uxbridge, Middlesex, England, 1972, in press.Google Scholar
  24. 23.
    Scatchard, G., Ann. N.Y. Acad. Sci., 51: 660, 1949-CrossRefGoogle Scholar
  25. 24.
    Ekins, R.P., Newman, G.B., and O’Riordan, J.L.H., in R. L. Hayes, F.A. Goswitz, and B.E.P. Murphy (eds.), Radioisotopes in Medicine: In Vitro Studies, U.S. Atomic Energy Commission, Oak Ridge, p. 59, 1968.Google Scholar
  26. 25.
    Rodbard, D., Ruder, H.J., Vaitukaitis, J., Jacobs, H.S., J. Clin. Endocr., 33: 343, 1971.PubMedCrossRefGoogle Scholar
  27. 26.
    Rodbard, D., Catt, K. J., J. Steroid Biochem., 3: 255, 1972.PubMedCrossRefGoogle Scholar
  28. 27.
    Saroff, H.A., Minton, A.P., Science, 175: 1253, 1972.PubMedCrossRefGoogle Scholar
  29. 28.
    House, P.D.R., FEBS Letters, 16: 339, 1971.PubMedCrossRefGoogle Scholar
  30. 29.
    Vassent, G., Jard, S., C.R. Acad. Sci., Paris, 272: 880, 1971.Google Scholar
  31. 30.
    Vassent, G., C.R. Acad. Sci., Paris, 273: 113, 1971.Google Scholar
  32. 31.
    Vassent, G., C. R. Acad. Sci., Paris, 273: 2l6l, 1971.Google Scholar
  33. 32.
    Ogata, R.T., McConnell, H.M., Proc. Nat. Acad. Sci. U.S., 69: 335, 1972.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • D. Rodbard
    • 1
  • R. E. Bertino
    • 2
  1. 1.Reproduction Research Branch, National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  2. 2.Kalamazoo CollegeKalamazooUSA

Personalised recommendations