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Abstract

An increasing proportion of the pharmaceutical armamentarium will in future be composed of peptides and proteins, whether natural or synthetic in origin or, more likely, produced by recombinant DNA technology. Most peptides and proteins are not absorbed to any significant extent by the oral route and most available formulations of protein pharmaceuticals are therefore parenteral products for injection or inhalation (Table 11.1). The object of this chapter is to provide some background for the appreciation of the pharmaceutics of proteins and peptides as therapeutic entities. From an understanding of the nature of amino acids and their physical properties comes an appreciation of the physical nature and properties of polymerised amino acids – peptides, polypeptides and proteins, defined below. The solution properties of proteins in simple and complex media should be understood, together with the factors affecting the stability of proteins in solution. Problems in the formulation of proteins to be overcome will then become clearer.

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Further reading

  • R. Oliyar and V. J. Stella. 'Prodrugs of peptides and proteins for improved formulation and delivery.' Ann. Rev. Pharmacol. Toxicol. 32, 521 (1993)

    Article  Google Scholar 

  • M. C. Manning, K. Patel and R. T. Borchardt. 'Stability of protein pharmaceuticals.' Pharm. Res. 6, 903 ( 1989)

    Article  CAS  PubMed  Google Scholar 

  • J. L. Cleland, M. F. Powell and S. J. Shire. 'The development of stable protein formulations: a close look at protein aggregation, deoxidation and oxidation.' Crit. Rev. Therap. Drug Carrier Systems 10, 307 (1993)

    CAS  Google Scholar 

References

  1. T. E. Creighton, Proteins. 2nd edn, W. H. Freeman, New York, 1993

    Google Scholar 

  2. F. Flam. Science 263, 1562 (1994)

    Article  Google Scholar 

  3. D. Dressler and H. Potter. Discovering Enzymes. Scientific American Library, New York, 1991

    Google Scholar 

  4. J. L. Cleland, M. F. Powell and S. J. Shire. Crit. Rev. Ther. Drug Carrier Systems 10, 307 (1993)

    CAS  Google Scholar 

  5. M. C. Manning, K. Patel and R. T. Borchardt. Pharm. Res. 6, 903 (1989)

    Article  CAS  PubMed  Google Scholar 

  6. Y-C. J. Wang and M.A. Hanson. J. Parenter. Sci. Technol. 42, S2 (1988)

    Google Scholar 

  7. T. Chen. Drug Dev. Indust. Pharm. 18, 311 (1992)

    Article  Google Scholar 

  8. J. Brange, D.R. Owens, S. Kang and A. Volund. Diabetes Care 13, 923 (1990)

    Article  CAS  PubMed  Google Scholar 

  9. J. Brange, K. Drejer, J. F. Hansen, S. Havelund, M. C. Kaarsholm, S. G. Melberg and A. R. Sorensen. In Advances in Protein Design, International Workshop 1988 (H. Blocker, J. Collins, R. D. Schmid and D. Schomburg, eds), Chemie Weinheim, Basel, Switzerland, 1989, p. 139

    Google Scholar 

  10. D. N. Brems, P. L. Brown, C. Bryant et al. In Protein Folding: In Vivo and In Vitro (J. Cleland, ed.), ACS Symposium Series, Vol. 526, American Chemical Society, Washington, DC, 1993, p. 254

    Chapter  Google Scholar 

  11. Z. Shao, Y. Li, R. Krishnamoorthy, T. Chermak and A. K. Mitra. Pharm. Res. 10, 243 (1993)

    Article  CAS  PubMed  Google Scholar 

  12. A. B. Robinson and C. J. Rudd. In Current Topics in Cellular Regulation, Vol. 8 (B. L. Horecker and E. R. Stadtman, eds), Academic Press, New York, 1974, p.247

    Google Scholar 

  13. J. W. Scotchler and A. B. Robinson. Anal. Biochem. 59, 319 (1947)

    Article  Google Scholar 

  14. T. Geiger and S. Clarke. J. Bioi. Chern. 262, 785 (1987)

    CAS  Google Scholar 

  15. J. B. Gilbert, C. E. Price and J.P. Greenstein. J. Bioi. Chern. 180, 209 (1949)

    CAS  Google Scholar 

  16. S. Capasso, L. Mazzarella and A. Zagari. Peptide Res. 4 (1991)

    Google Scholar 

  17. J. H. McKerrow and A. B. Robinson. Anal. Biochem. 42, 565 (1971)

    Article  CAS  PubMed  Google Scholar 

  18. K. Patel and R. T. Borchardt. Pharm. Res. 7, 703 (1990)

    Article  CAS  PubMed  Google Scholar 

  19. T. Flatmark. Acta Chern. Scand. 20, 1487 (1966)

    Article  CAS  Google Scholar 

  20. R. Tyler-Cross and V. Schirch. J. Bioi. Chern. 266, 2549 (1991)

    Google Scholar 

  21. T.V. Brennan and S. Clarke. Protein Sci. 2, 331 (1993)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. B. Halliwell and M. C. Gutteridge. In Methods in Enzymology, Vol. 186. Free Radicals and Metal Ions in Human Disease, Academic Press, New York, 1990

    Google Scholar 

  23. C. M. Hariss and R. J. Hill. J. Bioi. Chern. 244, 2195 (1969)

    Google Scholar 

  24. V. Holeysovosky and M. Lazdunski. Biochim. Biophys. Acta 154, 457 (1968)

    Article  Google Scholar 

  25. T. P. Link and G. R. Start. J. Bioi. Chem. 243, 1082 (1968)

    CAS  Google Scholar 

  26. W. J. Ray, Jr. and D. E. Koshland, Jr. Brookhaven Symp. Bioi. 13, 135 (1960)

    Google Scholar 

  27. K. Kido and B. Kassel. Biochemistry 14, 631 (1975)

    Article  CAS  PubMed  Google Scholar 

  28. J. Jauregui-Adell and P. Jolles. Bull. Soc. Chim. Bioi. 46, 141 (1964)

    CAS  Google Scholar 

  29. J. D. Spikes and R. Straight. Ann. Rev. Phys. Chem. 18, 409 (1967)

    Article  CAS  Google Scholar 

  30. G. E. Means and R. E. Feeney. Chemical Modification of Proteins, Holden-Day Inc., San Francisco, 1971, p. 35

    Google Scholar 

  31. B. M. Wallace and J. S. Lasker. Science 260, 912 (1993)

    Article  CAS  PubMed  Google Scholar 

  32. D. A. Paterson, R. A. Conradi, A. R. Hilgers et al. Quantitative Structure-Action Relationships, 13, 4 (1994)

    CAS  Google Scholar 

  33. J. L. Cleland and R. Langer. In Formulation and Delivery of Proteins and Peptides (J. L. Cleland and R. Langer, eds), American Chemical Society, Washington, 1994, p.1

    Chapter  Google Scholar 

  34. J. R. Costantino, R. Langer and A. M. Klibanov. Biotechnology 13, 493 (1995)

    Article  CAS  PubMed  Google Scholar 

  35. M. J. Hageman, P. L. Possert and J. M. Bauer. J. Agric. Food Chem. 40, 342 (1992)

    Article  CAS  Google Scholar 

  36. G. Zografi. Drug. Dev. Ind. Pharm. 14, 1905 (1988)

    Article  CAS  Google Scholar 

  37. R. Arvinte, A. Cudd and A. F. Drake. J. Bioi. Chem. 268, 6415 (1993)

    CAS  Google Scholar 

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© 1998 A. T. Florence and D. Attwood

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Florence, A.T., Attwood, D. (1998). Peptides and Proteins. In: Physicochemical Principles of Pharmacy. Palgrave, London. https://doi.org/10.1007/978-1-349-14416-7_12

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  • DOI: https://doi.org/10.1007/978-1-349-14416-7_12

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