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Serum Stability of Peptides

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Peptide-Based Drug Design

Part of the book series: Methods In Molecular Biology™ ((MIMB,volume 494))

Summary

Hospitals worldwide have lately reported a worrying increase in the number of isolated drug-resistant pathogenic microbes. This has to some extent fueled at least academic interest in design and development of new lead components for novel drug design. Much of this interest has been focused on antimicrobial peptides and peptides in general, primarily due to their natural occurrence and low toxicity. However, issues have been raised regarding the stability of peptide therapeutics for systemic use. The focus of this chapter is assays for measuring peptide stability in the presence of serum, both in vitro and in vivo.

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References

  1. Overbye, K.M., and Barrett, J.F. (2005) Antibiotics: where did we go wrong? Drug Discov. Today 10, 45–52.

    Article  PubMed  Google Scholar 

  2. Levy, S.B., and Marshall, B. (2004) Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 10(12 Suppl.), S122–129.

    Article  CAS  PubMed  Google Scholar 

  3. Gallwitz, B. (2005) New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins. Rev Diabet Stud. 2,61–69.

    Article  PubMed  Google Scholar 

  4. Martinez, N.R., Augstein, P., Moustakas, A.K., et al. (2003) Disabling an integral CTL epitope allows suppression of autoimmune diabetes by intranasal proinsulin peptide. J. Clin. Invest. 111, 1365–1371.

    CAS  PubMed  Google Scholar 

  5. Cohen, I.R. (2002) Peptide therapy for type I diabetes: the immunological homunculus and the rationale for vaccination. Diabetologia 45, 1468–1474.

    Article  CAS  PubMed  Google Scholar 

  6. Raz, I., Elias, D., Avron, A., Tamir, M., Metzger, M., and Cohen, I.R. (2001) Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet 24,1749–1753.

    Article  Google Scholar 

  7. Myers, L.K., Sakurai, Y., Tang, B., et al. (2002) Peptide-induced suppression of collagen-induced arthritis in HLA-DR1 transgenic mice. Arthritis Rheum. 46, 3369–3377.

    Article  CAS  PubMed  Google Scholar 

  8. Lorey, S., Stockel-Maschek, A., Faust, J., et al. (2003) Different modes of dipeptidyl peptidase IV (CD26) inhibition by oligopeptides derived from the N-terminus of HIV-1 Tat indicate at least two inhibitor binding sites. Eur. J. Biochem. 270, 2147–2156.

    Article  CAS  PubMed  Google Scholar 

  9. Vincent, B., Jiracek, J., Noble, F., et al. (1997) Effect of a novel selective and potent phosphinic peptide inhibitor of endopeptidase 3.4.24.16 on neurotensin-induced analgesia and neuronal inactivation. Br. J. Pharmacol. 121, 705–710.

    Article  CAS  PubMed  Google Scholar 

  10. Fridkis-Hareli, M., Santambrogio, L., Stern, J.N., Fugger, L., Brosnan, C., and Strominger, J.L. (2002) Novel synthetic amino acid copolymers that inhibit autoantigen-specific T cell responses and suppress experimental autoimmune encephalomyelitis. J. Clin. Invest. 109, 1635–1643.

    CAS  PubMed  Google Scholar 

  11. Jenssen, H., Hamill, P., and Hancock, R.E.W. (2006) Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491–511.

    Article  CAS  PubMed  Google Scholar 

  12. Watt, P.M. (2006) Screening for peptide drugs from the natural repertoire of biodiverse protein folds. Nat. Biotechnol. 24, 177–183.

    Article  CAS  PubMed  Google Scholar 

  13. Bush, K., Macielag, M., and Weidner-Wells, M. (2004) Taking inventory: antibacterial agents currently at or beyond phase 1. Curr. Opin. Microbiol. 7, 466–476.

    Article  CAS  PubMed  Google Scholar 

  14. Ge, Y., MacDonald, D.L., Holroyd, K.J., Thornsberry, C., Wexler, H., and Zasloff, M. (1999) In vitro antibacterial properties of pexiganan, an analog of magainin. Antimicrob. Agents Chemother. 43, 782–788.

    CAS  PubMed  Google Scholar 

  15. Hoffmann, R., Bulet, P., Urge, L., and Otvos, L., Jr. (1999) Range of activity and metabolic stability of synthetic antibacterial glycopeptides from insects. Biochim. Biophys. Acta 1426, 459–467.

    CAS  PubMed  Google Scholar 

  16. Howl, J., ed. (2005) Peptide Synthesis and Applications. Totowa, NJ: Humana Press.

    Google Scholar 

  17. Rekdal, O., Andersen, J., Vorland, L.H., and Svendsen, J.S. (1999) Construction and synthesis of lactoferricin derivatives with enhanced antibacterial activity. J. Pept. Sci. 5, 32–45.

    Article  CAS  Google Scholar 

  18. Sato, A.K., Viswanathan, M., Kent, R.B., and Wood, C.R. (2006) Therapeutic peptides: technological advances driving peptides into development. Curr. Opin. Biotechnol. 17, 638–642.

    Article  CAS  PubMed  Google Scholar 

  19. Landon, L.A., Zou, J., and Deutscher, S.L. (2004) Is phage display technology on target for developing peptide-based cancer drugs? Curr. Drug Discov. Technol. 1, 113–132.

    Article  CAS  PubMed  Google Scholar 

  20. Powell, M.F., Stewart, T., Otvos, L, Jr., et al. (1993) Peptide stability in drug development. II. Effect of single amino acid substitution and glycosylation on peptide reactivity in human serum. Pharm. Res. 10, 1268–1273.

    Article  CAS  PubMed  Google Scholar 

  21. Otvos, L., Jr., Urge, L., Xiang, Z.Q., et al. (1994) Glycosylation of synthetic T helper cell epitopic peptides influences their antigenic potency and conformation in a sugar location-specific manner. Biochim. Biophys. Acta 1224,68–76.

    Article  CAS  PubMed  Google Scholar 

  22. Otvos, L., Jr., Cappelletto, B., Varga, I., et al. (1996) The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes. Biochim. Biophys. Acta 1313, 11–19.

    Article  PubMed  Google Scholar 

  23. Veronese, F.M., and Pasut, G. (2005) PEGylation, successful approach to drug delivery. Drug Discov. Today 10, 1451–1458.

    Article  CAS  PubMed  Google Scholar 

  24. Werle, M., and Bernkop-Schnurch, A. (2006) Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids 30, 351–367.

    Article  CAS  PubMed  Google Scholar 

  25. Leger, R., Thibaudeau, K., Robitaille, M., et al. (2004) Identification of CJC-1131-albumin bioconjugate as a stable and bioactive GLP-1(7–36) analog. Bioorg. Med. Chem. Lett. 14, 4395–4398.

    Article  CAS  PubMed  Google Scholar 

  26. Dumont, J.A., Low, S.C., Peters, R.T., and Bitonti, A.J. (2006) Monomeric Fc fusions: impact on pharmacokinetic and biological activity of protein therapeutics. BioDrugs 20, 151–160.

    Article  CAS  PubMed  Google Scholar 

  27. Murillo, L., Piot, J.M., Coitoux, C., and Fruitier-Arnaudin, I. (2006) Brain processing of hemorphin-7 peptides in various subcellular fractions from rats. Peptides 27, 3331–3340.

    Article  CAS  PubMed  Google Scholar 

  28. McDermott, J.R., Smith, A.I., Biggins, J.A., Hardy, J.A., Dodd, P.R., and Edwardson, J.A. (1981) Degradation of luteinizing hormone-releasing hormone by serum and plasma in vitro. Regul. Pept. 2, 69–79.

    Article  CAS  PubMed  Google Scholar 

  29. Walter, R., Neidle, A., and Marks, N. (1975) Significant differences in the degradation of pro-leu-gly-NH2 by human serum and that of other species (38484). Proc. Soc. Exp. Biol. Med. 148, 98–103.

    CAS  PubMed  Google Scholar 

  30. Springer, C.J., Eberlein, G.A., Eysselein, V.E., Schaeffer, M., Goebell, H., and Calam, J. (1991) Accelerated in vitro degradation of CCK-58 in blood and plasma of patients with acute pancreatitis. Clin Chim Acta. 198, 245–253.

    Article  CAS  PubMed  Google Scholar 

  31. White, N., Griffiths, E.C., Jeffcoate, S.L., Milner, R.D.G., Preece, M.A. (1980) Age-related changes in the degradation of thyrotrophin releasing hormone by human and rat serum. J. Endocrin. 86, 397–402.

    Article  CAS  Google Scholar 

  32. Frohman, L.A., Downs, T.R., Williams, T.C., Heimer, E.P., Pan, Y.C., and Felix, A.M. (1986) Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J. Clin. Invest. 78, 906–913.

    Article  CAS  PubMed  Google Scholar 

  33. Wroblewski, V.J. (1991) Mechanism of deiodination of 125I-human growth hormone in vivo. Relevance to the study of protein disposition. Biochem. Pharmacol. 42, 889–897.

    Article  CAS  PubMed  Google Scholar 

  34. Cudic, M., Lockatell, C.V., Johnson, D.E., and Otvos, L., Jr. (2003) In vitro and in vivo activity of an antibacterial peptide analog against uropathogens. Peptides 24, 807–820.

    Article  CAS  PubMed  Google Scholar 

  35. Otvos, L., Jr., Snyder, C., Condie, B., Bulet, P., and Wade, J.D. (2005) Chimeric antimicrobial peptides exhibit multiple modes of action. Int. J. Pept. Res. Ther. 11, 29–42.

    Article  CAS  Google Scholar 

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© 2008 Humana Press, a part of Springer Science+Business Media, LLC

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Jenssen, H., Aspmo, S.I. (2008). Serum Stability of Peptides. In: Otvos, L. (eds) Peptide-Based Drug Design. Methods In Molecular Biology™, vol 494. Humana Press. https://doi.org/10.1007/978-1-59745-419-3_10

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  • DOI: https://doi.org/10.1007/978-1-59745-419-3_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-990-1

  • Online ISBN: 978-1-59745-419-3

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