Summary
Identification of antibody binding peptides may be based on the primary structure of the protein antigens used to raise the antibodies (knowledge- or sequence-based approach). This involves scanning the entire sequence of the antigen with overlapping peptides (peptide scan), which are then probed for binding to the respective antibody. If a natural protein binding partner is not known, one has to use combinatorial synthetic libraries with peptide mixtures, randomly generated chemically synthesized libraries of single individual sequences, or biologically produced libraries (e.g., phage display libraries, see Chapter “Epitope Mapping Using Phage Display Peptide Libraries”). This chapter describes chemically synthesized combinatorial, as well as randomly generated peptide libraries, collectively called de novo approaches, and their application for antibody epitope mapping.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lebl, M. (1999) Parallel personal comments on “classical” papers in combinatorial chemistry. J. Comb. Chem. 1, 3–24.
Beck-Sickinger, A. G. and Jung, G. (1996) From multiple peptide synthesis to peptide libraries, in Combinatorial Peptide and Nonpeptide Libraries (Jung, G., ed.), VCH Verlagsgesellschaft, Weinheim, Germany, pp. 79–109.
Furka, A. (1996) Chemical synthesis of peptide libraries, in Combinatorial Peptide and Nonpeptide Libraries (Jung, G., ed.), VCH Verlagsgesellschaft, Weinheim, Germany, pp. 111–137.
Furka, A., Sebestyen, F., Asgedom, M., and Dibo, G. (1991) General method for rapid synthesis of multicomponent peptide mixtures. Int. J. Pept. Protein Res. 37, 487–493.
Lam, K. S., Salmon, S. E., Hersh, E. M., Hruby, V. J., Kazmierski, W. M., and Knapp, R. J. (1991) A new type of synthetic peptide library for identifying ligand-binding activity. Nature 354, 82–84.
Lebl, M., Krchnak, V., Sepetov, N. F., Seligmann, B., Strop, P., and Felder, S. (1995) One-bead-one-structure combinatorial libraries. Biopolymers 37, 177–198.
Pinilla, C., Appel, J., Dooley, C., Blondelle, S., Eichler, J., Dörner, B., Ostresh, J., and Houghten, R. A. (1996) The versatility of non-support bound combinatorial libraries, in Combinatorial Peptide and Nonpeptide Libraries (Jung, G., ed.), VCH Verlagsgesellschaft, Weinheim, Germany, pp. 139–172.
Pinilla, C., Appel, J. R., Blanc, P., and Houghten, R. A. (1992) Rapid identification of high affinity peptide ligands using positional scanning synthetic peptide combinatorial libraries. Biotechniques 13, 901–905.
Frank, R. and Overwin, H. (1996) SPOT Synthesis: epitope analysis with arrays of synthetic peptides prepared on cellulose membranes, in Methods in Molecular Biology Epitope Mapping Protocols (Morris, G. E., ed.), Humana Press, Totowa, NJ, vol. 66, pp. 149–169.
Houghten, R. A., Pinilla, C., Blondelle, S. E., Appel, J. R., Dooley, C. T., and Cuervo, J. H. (1991). Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery. Nature 354, 84–86.
Houghten, R. A., Appel, J. R., Blondelle, S. E., Cuervo, J. H., Dooley, C. T., and Pinilla, C. (1992). The use of synthetic peptide libraries for the identification of bioactive peptides. Biotechniques 13, 412–421.
Kramer, A., Volkmer-Engert, R., Malin, R., Reineke, U., and Schneider-Mergener, J. (1993) Simultaneous synthesis of peptide libraries on single resin and continuous cellulose membrane supports: examples for the identification of protein, metal and DNA binding peptide mixtures. Peptide Res. 6, 314–319.
Kramer, A., Schuster, A., Reineke, U., Malin, R., Volkmer-Engert, R., Landgraf, C., and Schneider-Mergener, J. (1994) Combinatorial cellulose-bound peptide libraries: screening tools for the identification of peptides that bind ligands with predefned specifcity. Methods: A Companion to Methods Enzymol. 6, 912–921.
Schneider-Mergener, J., Kramer, A., and Reineke, U. (1996) Peptide libraries bound to continuous cellulose membranes: tools to study molecular recognition, in Combinatorial Libraries: Synthesis, Screening and Application Potential (Cortese, R., ed.), Walter de Gruyter, Berlin, Germany, pp. 53–68.
Kramer, A., Keitel, T., Winkler, K., Stöcklein, W., Höhne, W., and Schneider-Mergener, J. (1997) Molecular basis for the binding promiscuity of an anti-p24 (HIV-1) monoclonal antibody. Cell 91, 799–809.
Blake, J. and Litzi-Davis, L. (1992) Evaluation of peptide libraries: an iterative strategy to analyze the reactivity of peptide mixtures with antibodies. Bioconjugate Chem. 3, 510–513.
Kramer, A., Vakalopoulou, E., Schleuning, W. D., and Schneider-Mergener, J. (1995) A general route to fingerprint analyses of peptide-antibody interactions using a clustered amino acid peptide library: comparison with a phage display library. Mol. Immunol. 32, 459–465.
Pirrung, M. C. and Chen, J. (1995) Preparation and screening against acetylcholinesterase of a non-peptide “indexed” combinatorial library. J. Am. Chem. Soc. 117, 1240–1245.
Déprez, B., Willard, X., Bourel, L., Coste, H., Hyafil, F., and Tartar, A. (1995) Orthogonal combinatorial chemical libraries. J. Am. Chem. Soc. 117, 5405–5406.
Reineke, U., Ivascu, C., Schlief, M., Landgraf, C., Gericke, S., Zahn, G., Herzel, H., Volkmer-Engert, R., and Schneider-Mergener, J. (2002) Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences. J. Immunol. Methods 267, 37–51.
Slootstra, J. W., Puijk, W. C., Ligtvoet, G. J., Langeveld, J. P. M., and Meloen, R. H. (1995) Structural aspects of antibody-antigen interaction revealed through small random peptide libraries. Mol. Divers. 1, 87–96.
Slootstra, J. W., Puijk, W. C., Ligtvoet, G. J., Kuperus, D., Schaaper, W. M. M., and Meloen, R. H. (1997) Screening of a small set of random peptides: a new strategy to identify synthetic peptides that mimic epitopes. J. Mol. Recognit. 10, 217–224.
van der Veen, P. J., Wessels, L. F. A., Slootstra, J. W., Meloen, R. H., Reinders, M. J. T., and Hellendoorn, J. (2001) Determination of binding amino acids based on random peptide array screening data, in Lecture Notes in Computer Science, Workshop on Algorithms in Bioinformatics (WABI 2001), (Gascuel, O. and Moret, B. M. E., eds.), Springer-Verlag, Berlin, Heidelberg, Germany, pp. 264–277.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Reineke, U. (2009). Antibody Epitope Mapping Using De Novo Generated Synthetic Peptide Libraries. In: Schutkowski, M., Reineke, U. (eds) Epitope Mapping Protocols. Methods in Molecular Biology™, vol 524. Humana Press. https://doi.org/10.1007/978-1-59745-450-6_14
Download citation
DOI: https://doi.org/10.1007/978-1-59745-450-6_14
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-934115-17-6
Online ISBN: 978-1-59745-450-6
eBook Packages: Springer Protocols