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Molecular Design: Theoretical and Solution Studies on Copper(II) Complex of Glycylglycyl-L-Histidine-N-Methyl Amide, A Peptide Designed to Mimic The Copper(II)-Transport Site of Human Albumin

  • Bibudhendra Sarkar
  • V. Renugopalakrishnan
  • Theo P. A. Kruck
  • Show-Jy Lau
Part of the The Jerusalem Symposia on Quantum Chemistry and Biochemistry book series (JSQC, volume 8)

Abstract

The molecular architecture around the metal binding site of a protein clearly reveals the nature of the participating ligands and the associated coordination geometry. Recent studies [1–5] have shown that, once the biological nature of metal transport mechanism is known and the metal binding site is identified, one can design and synthesize a small molecule which mimics the specific macromolecular binding site but excludes a large extraneous section of the molecule. Such a molecule has the specificity and binding affinity very similar to those of the native macromolecule. It is envisaged that such a designed molecule may find, in future, important biomedical applications. In this communication, we wish to report the molecular design of a peptide amide: Glycylglycyl-L-histidine-N-methyl amide mimicking the specific Cu(II)-transport site of human albumin. Theoretical calculations were implemented to aid the design, and solution studies were undertaken to compare the Cu(II)-binding properties between the designed molecule and the native binding site.

Keywords

Torsional Angle Molecular Design Human Albumin Metal Binding Site Transport Site 
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.
    Sarkar, B.: Proceedings of the 15 th Canadian Federation of Biological Societies, Quebec, Canada, 1972, p. 659.Google Scholar
  2. 2.
    Sarkar, B.: Proceedings of the 9th International Congress of Biochemistry, Stockholm, Sweden, 1973, p. 122.Google Scholar
  3. 3.
    Sarkar, B.: Proceedings of the 16th International Conference on Coordination Chemistry, Dublin, Ireland, 1974, p. S2.Google Scholar
  4. 4.
    Lau, S., Kruck, T. P. A., and Sarkar, B.: J. Biol. Chem. 2A9, 5878 (1974).Google Scholar
  5. 5.
    Lau, S. and Sarkar, B.: Can. J. Chem. due March 53, 710 (1975).CrossRefGoogle Scholar
  6. 6.
    Peters, T., Jr. and Blumenstock, F. A.: J. Biol. Chem. 242, 1574 (1967).Google Scholar
  7. 7.
    Appleton, D. W. and Sarkar, B.: J. Biol. Chem. 246, 5040 (1971).Google Scholar
  8. 8.
    Shearer, W. T., Bradshaw, R. A., Gurd, F. R. N., and Peters, T., Jr.: J. Biol. Chem. 242, 5451 (1967).Google Scholar
  9. 9.
    Dixon, J. W. and Sarkar, B.: Biochem. Biophys. Res. Comm. 48, 197 (1972).CrossRefGoogle Scholar
  10. 10.
    Dixon, J. W. and Sarkar, B.: J. Biol. Chem. 249, 5872 (1974).Google Scholar
  11. 11.
    Pullman, B. and Pullman, A.: in C. B. Anfinsen, J. T. Edsall, and F. M. Richards (eds.), Advances in Protein Chemistry 28, Academic Press, New York and London, 1974, p. 347.Google Scholar
  12. 12.
    Ramachandran, G. N. and Sasisekharan, V.: in C. B. Anfinsen, J. T. Edsall, M. L. Anson, and F. M. Richards (eds.), Advances in Protein Chemistry 23, Academic Press, New York and London, 1968, p. 283.Google Scholar
  13. 13.
    Freeman, H. C.: in C. B. Anfinsen, J. T. Edsall, M. L. Anson, and F. M. Richards (eds.), Advances in Protein Chemistry 22, Academic Press, New York and London, 1967, p. 257.Google Scholar
  14. 14.
    Renugopalakrishnan, V., Renugopalakrishnan, M., and Sarkar, B.: International Journal of Quantum Chemistry Symposium Proc, in press (1975).Google Scholar
  15. 15.
    Sarkar, B. and Kruck, T. P. A.: Can. J. Chem. 51, 3541 (1973).CrossRefGoogle Scholar
  16. 16.
    Sarkar, B.: Proceedings of the 3rd International Symposium on Wilson’s Disease, Paris, France, 1973, p. 5.Google Scholar
  17. 17.
    Walshe, J. M.: Am. J. Med. 21, 487 (1956).CrossRefGoogle Scholar
  18. 18.
    Walshe, J. M.: Quart. J. Med. 42, 441 (1973).Google Scholar
  19. 19.
    Renugopalakrishnan, V. and Sarkar, B.: Fed. Proc. (U.S.A.) 33, 1265 (1974).Google Scholar

Copyright information

© D. Reidel Publishing Company, Dordrecht-Holland 1976

Authors and Affiliations

  • Bibudhendra Sarkar
    • 1
  • V. Renugopalakrishnan
    • 1
  • Theo P. A. Kruck
    • 1
  • Show-Jy Lau
    • 1
  1. 1.The Research Institute, The Hospital for Sick Children, Toronto and The Dept. of BiochemistryUniversity of TorontoTorontoCanada

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