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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Overbye, K.M., and Barrett, J.F. (2005) Antibiotics: where did we go wrong? Drug Discov. Today 10, 45–52.
Levy, S.B., and Marshall, B. (2004) Antibacterial resistance worldwide: causes, challenges and responses. Nat Med. 10(12 Suppl.), S122–129.
Gallwitz, B. (2005) New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins. Rev Diabet Stud. 2,61–69.
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.
Cohen, I.R. (2002) Peptide therapy for type I diabetes: the immunological homunculus and the rationale for vaccination. Diabetologia 45, 1468–1474.
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.
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.
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.
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.
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.
Jenssen, H., Hamill, P., and Hancock, R.E.W. (2006) Peptide antimicrobial agents. Clin. Microbiol. Rev. 19, 491–511.
Watt, P.M. (2006) Screening for peptide drugs from the natural repertoire of biodiverse protein folds. Nat. Biotechnol. 24, 177–183.
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.
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.
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.
Howl, J., ed. (2005) Peptide Synthesis and Applications. Totowa, NJ: Humana Press.
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.
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.
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.
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.
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.
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.
Veronese, F.M., and Pasut, G. (2005) PEGylation, successful approach to drug delivery. Drug Discov. Today 10, 1451–1458.
Werle, M., and Bernkop-Schnurch, A. (2006) Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids 30, 351–367.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
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
Download citation
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
eBook Packages: Springer Protocols