Abstract
The modular nature of peptides can be exploited in the synthesis of chimeric sequences that combine diverse motifs in a single molecule. A theoretical consideration of the classification of peptides further expounds the multigeneric nature of peptide chimeras. Strategies for chimeric peptide syntheses include the chemical cross-linking of monomers and tandem combination by conventional SPPS. Additional details of chimeric peptide synthesis are also provided elsewhere in this volume. This chapter also explores some of the more common applications of chimeric peptides with particular emphasis on the molecular pharmacology of sequences that include address motifs for G protein-coupled receptors. Specific details of the biological properties of chimeras containing mastoparan, an amphiphilic tetradecapeptide component of wasp venom, further illustrate the novel and often unpredictable biological actions of chimeric constructs. These and numerous additional studies confirm that chimerism is an established strategy for the synthesis of molecular probes and bioactive agents.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Woolfson, A. (2000) Life Without Genes. Harper Collins, London, U.K.
Manning, M., Bankowski, K., and Sawyer W. H. (1987) Selective agonists and antagonists of vasopressin, in Vasopressin (Gash, D. M. and Boer, G. J., eds.), Plenum Press, New York, pp. 335–368.
Stewart, J.M. (1995) Bradykinin antagonists: developments and applications. Biopolymers 37, 143–155.
Howl, J. and Payne, S. J. (2003) Bradykinin receptors as a therapeutic target. Expert Opin. Ther. Targets 7, 277–285.
Howl, J. and Wheatley, M. (1995) Molecular pharmacology of V1a vasopressin receptors. Gen. Pharmacol. 26, 1143–1152
Gitelman, H. J., Kalpper, D. G., Alderman, F. R., and Blythe, W. B. (1980) Ala-Gly and Val-Asp-[Arg8]-vasopressin: Bovine storage forms of arginine vasopressin with natriuretic activity. Science 207, 893–896.
Valkna, A., Laidmä, E., Karelson, E., Zilmer, M., Juréus, A., and Langel, . (1995) Effects of chimeric galanin receptor ligands on basal adenylate cyclase activity in rat ventral hippocampal membranes. Protein Pept. Lett. 2, 267–274.
Östenson, C.-G., Zaitsev, S., Berggren, P.-G., Efendic, S., Langel, ., and Bartfai, T. (1997) Galparan: a powerful insulin releasing chimeric peptide acting at a novel site. Endocrinology 138, 3308–3313.
Howl, J., Langel, ., Hawtin, S. R., et al. (1997) Chimeric strategies for the rational design of bioactive analogs of small peptide hormones. FASEB J. 11, 582–59
Howl, J., Yarwood, N. J., Stock, D., and Wheatley, M. (1996) Probing the V1a vasopressin receptor binding site with pyroglutamate-substituted linear peptide antagonists. Neuropeptides 30, 73–79.
Hällbrink, M., Saar, K., Östenson, C.-G., et al. (1999) Effects of vasopressinmastoparan chimeric peptides on insulin release and GTPase activity. Regul. Pept. 82, 45–51.
Longland, C. L., Mezna, M., Langel, ., et al. (1998) Biochemical mechanisms of calcium mobilisation induced by mastoparan and chimeric hormone-mastoparan constructs. Cell Calcium 24, 27–34.
Farquhar, M., Soomets, U., Bates, R. L., Martin, A., Langel, Ö., and Howl, J. (2002) Novel mastoparan analogs induce differential secretion from mast cells. Chem. & Biol. 9, 63–70.
Poyner, D. R., Soomets, U., Howitt, S. G., and Langel, Ö. (1998) Structural determinants for binding to CGRP receptors expressed by human SK-N-MC and Col 29 cells: studies with chimeric and other peptides. Br. J. Pharmacol. 124, 1659–1666
Wei, C. M., Kim C. H., Miller, V. M., and Burnett, J. C. (1993) Vasonatrin peptide-a unique synthetic natriuretic peptide and vasorelaxing peptide. J. Clin. Invest. 92, 2048–2052
Foran, S. E., Carr, D. B., Lipkowski, A. W., et al. (2000) A substance P-opioid chimeric peptide as a unique nontolerance-froming analgesic. Proc. Natl. Acad. Sci. USA 97, 7621–7626.
Miscika, A., Lipkowski, A. W., Horvath, R., Porreca, F., Yamamura, H. I., and Hruby, V. J. (1994) Delta-opioid receptor-selective ligands-DPLPE-deltorphin chimeric peptide analogs. Int. J. Pept. Protein Res. 44, 80–8
Gupta, S., Pasha, S., Gupta, Y. K., and Bhardwaj, D. K. (1999) Chimeric peptide of Met-enkaphilin and FMRFa induces antinociception and attenuates development of tolerance to morphine antinociception. Peptides 20, 471–478.
Rajott, D. and Ruoslahti, E. (1999) Membrane dipeptidase is the receptor for a lung-targeting peptide iodentified by in vivo phage display. J. Biol. Chem. 274, 11593–1159
Porkka, K., Laakkonen, P., Hoffman, J. A., Bernasconi, M., and Ruoslahti, E. (2002) A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc. Natl. Acad. Sci. USA 99, 7444–7449.
Laakkonen, P., Porkka, K., Hoffman, J. A., and Ruoslahti, E. A. (2002) Tumorhoming peptide with a targeting specificity related to lymphatic vessels. Nat. Med. 8, 751–75
Arap, W., Haedicke, W., Bernasconi, M., et al. (2002) Targeting the prostate for destruction through a vascular address. Proc. Natl. Acad. Sci USA 99, 1527–1531.
Åkerman, M. E., Chan, W. C., Laakonen, P., Bhatia, S., and Ruoslahti, E. (2002) Nanocrystal targeting in vivo. Proc. Natl. Acad. Sci. USA 99, 12617–12621.
Schally, A. V. and Nagy, A. (1999) Cancer chemotherapy based on targeting of cytotoxic peptide conjugates to their receptor on tumours. Eur. J. Endocrinol. 141, 1–14
Cheronis, J. C., Whalley, E. T., Allen, L. G., et al. (1994) Design, synthesis and in vitro activity of bis(succinimido)hexane peptide heterodimers with combined B1 and B2 antagonist activity. J. Med. Chem. 37, 348–355.
Chan, D., Gera, L., Stewart, J., et al. (2002) Bradykinin antagonist dimer, CU210, inhibits the growth of human lung cancer cell lines by a “biased agonist” mechanism. Proc. Natl. Acad. Sci. USA 99, 4608–4613.
Howl, J. and Wheatley, M. (1998) Biochemical pharmacology of total retroinverso analogues of bradykinin and angiotensin II: Molecular recognition by Gprotein-coupled receptors and angiotensin converting enzyme. Lett. Peptide Sci. 5, 37–41.
Howl, J. and Wheatley, M. (1993) V1a vasopressin receptors: Selective biotinylated probes. Meth. Neurosci. 13, 281–29
Howl, J., Yarwood, N. J., Davies, A. R. L., and Wheatley, M. (1996) Renal bradykinin and vasopressin receptors: Ligand selectivity and classification. Kidney Int. 50, 586–590
Halazy, S.(1999) G-protein coupled receptors bivalent ligands and drug design. Expert Opin. Ther. Pat. 9, 431–44
Bernatowicz, M. S., Matsueda, R., and Matsueda, G. R. (1986) Preparation of Boc-[S-(3-Nitro-2-pyridinesulfenyl)]-cysteine and its use for unsymmetrical disulfide bond formation. Int. J. Pept. Protein Res. 28, 107–11
Tam, J. P. and Spetzler, J. C. (1995) Chemoselective approaches to the preparation of peptide dendrimers and branched artificial proteins using unprotected peptides as building blocks. Biomedical Peptides, Proteins & Nucleic Acids 1, 123–132.
Pooga, M., Juréus, A., Rezaei, K., et al. (1998) Novel galanin receptor ligands. J. Peptide Res. 51, 65–7
Isersky, C., Metzger, H., and Buell, D. N. (1975) Cell cycle-associated changes in receptors for IgE during growth and differentiation of a rat basophilic leukemia cell line. J. Exp. Med. 141, 1147–1162.
Slaninová, J., Machová, A., Kuncarová, P., MaletĂnská, L., and Howl, J. (2001) Receptor affinity and biological activity of chimeric peptides combining bradykinin with arginine vasopressin of fibronectin-related RGD sequences, in 2nd Hellenic Forum on Bioactive Peptides (Cordopatis, P. A. ed.), Typorama, Patras, pp. 359–365.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Howl, J. (2005). Chimerism. In: Howl, J. (eds) Peptide Synthesis and Applications. Methods in Molecular Biology™, vol 298. Humana Press. https://doi.org/10.1385/1-59259-877-3:025
Download citation
DOI: https://doi.org/10.1385/1-59259-877-3:025
Publisher Name: Humana Press
Print ISBN: 978-1-58829-317-6
Online ISBN: 978-1-59259-877-9
eBook Packages: Springer Protocols