Abstract
Peptides are increasingly emerging as human therapeutic drugs. By screening very large phage display libraries, novel bioactive peptides that bind to the target of interest with desired biological properties can be identified. Peptides that are obtained in this fashion become the basis for therapeutic molecule development. However, naked peptides are usually not sufficient to be therapeutic molecules by themselves. They need to be chemically modified or conjugated to other molecules to obtain desired physicochemical and in vivo properties. In this chapter, we describe a general methodology of identifying bioactive peptides by biopanning of peptide phage libraries. As an example of therapeutic peptide modifications, we also describe a method for fusing the peptides to the Fc portion of antibody molecule to increase in vivo stability and activity.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Scott JK, Craig L (1994) Random peptide libraries. Curr Opin Biotechnol 5:40–48
Houghten RA (1994) Combinatorial libraries. Finding the needle in the haystack. Curr Biol 4:564–567
Smith GP, Petrenko VA (1997) Phage display. Chem Rev 97:391–410
Cortese R, Monaci P, Nicosia A, Luzzago A, Felici F, Galfré G et al (1995) Identification of biologically active peptides using random libraries displayed on phage. Curr Opin Biotechnol 6:73–80
Lowman HB (1997) Bacteriophage display and discovery of peptide leads for drug development. Annu Rev Biophys Biomol Struct 26:401–424
Markland W, Roberts BL, Saxena MJ, Guterman SK, Ladner RC (1991) Design, construction and function of a multicopy display vector using fusions to the major coat protein of bacteriophage M13. Gene 109:13–19
Li Z, Zhang J, Zhao R, Xu Y, Gu J (2005) Preparation of peptide-targeted phagemid particles using a protein III-modified helper phage. Biotechniques 39:493–497
Lien S, Lowman HB (2003) Therapeutic peptides. Trends Biotechnol 21:556–562
Veronese FM, Mero A (2008) The impact of PEGylation on biological therapies. BioDrugs 22:315–329
Takahashi-Nishioka T, Yokogawa K, Tomatsu S, Nomura M, Kobayashi S, Miyamoto K (2008) Targeted drug delivery to bone: pharmacokinetic and pharmacological properties of acidic oligopeptide-tagged drugs. Curr Drug Discov Technol 5:39–48
Houghten RA (1985) General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen–antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A 82: 5131–5135
Ladner RC, Sato AK, Gorzelany J, de Souza M (2004) Phage display-derived peptides as therapeutic alternatives to antibodies. Drug Discov Today 9:525–529
Krumpe L, Mori T (2006) The use of phage-displayed peptide libraries to develop tumor-targeting drugs. Int J Peptide Res Ther 12: 79–91
Sergeeva A, Kolonin MG, Molldrem JJ, Pasqualini R, Arap W (2006) Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev 58:1622–1654
Oliner J, Min H, Leal J, Yu D, Rao S, You E et al (2004) Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 6:507–516
Turková J (1999) Oriented immobilization of biologically active proteins as a tool for revealing protein interactions and function. J Chromatogr B Biomed Sci Appl 722:11–31
Hetian L, Ping A, Shumei S, Xiaoying L, Luowen H, Jian W et al (2002) A novel peptide isolated from a phage display library inhibits tumor growth and metastasis by blocking the binding of vascular endothelial growth factor to its kinase domain receptor. J Biol Chem 277:43137–43142
Kelley BD, Booth J, Tannatt M, Wu QL, Ladner R, Yu J et al (2004) Isolation of a peptide ligand for affinity purification of factor VIII using phage display. J Chromatogr A 1038:121–130
Hills R, Mazzarella R, Fok K, Liu M, Nemirovskiy O, Leone J et al (2007) Identification of an ADAMTS-4 cleavage motif using phage display leads to the development of fluorogenic peptide substrates and reveals Matrilin-3 as a novel substrate. J Biol Chem 282:11101–11109
Acknowledgement
This work was supported by Samsung Electronics Co., Ltd.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Ryu, J.S., Cho, A.Y., Seo, S.W., Min, H. (2014). Engineering Bioactive Peptide-Based Therapeutic Molecules. In: Nixon, A. (eds) Therapeutic Peptides. Methods in Molecular Biology, vol 1088. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-673-3_3
Download citation
DOI: https://doi.org/10.1007/978-1-62703-673-3_3
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-672-6
Online ISBN: 978-1-62703-673-3
eBook Packages: Springer Protocols