Abstract
Cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. Owing to the robustness of amide bond chemistry, the ability to explore extensive chemical diversity by incorporation of unnatural and natural amino acids, and the ability to explore conformational diversity, through the incorporation of various constraints, arrays of cyclic peptides can be tailored to broadly sample chemical diversity. We describe the combination of a safety catch linker with a directed-sorted procedure for the synthesis of large arrays of diverse cyclic peptides for high-throughput screening.
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References
Horton, D. A., Bourne, G. T., and Smythe, M. L. (2002) Exploring privileged structures: the combinatorial synthesis of cyclic peptides. J. Comp-Aided Mol. Des. 16, 415–430.
MacDonald, M. and Aube, J. (2001) Approaches to cyclic peptide β-turn mimics. Curr. Org. Chem. 5, 417–438.
Emmel, E. A., Verweij, C. L., Durand, D. B., Higgins, K. M., Lacy, E., and Crabtree, G. R. (1989) Cyclosporine-A specifically inhibits function of nuclear proteins involved in T-cell activation. Science 246, 1617–1620.
Mootz, H. D. and Marahiel, M. A. (1997) The tyrocidine biosynthesis operon of Bacillus brevis: complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J. Bacteriol. 179, 6843–6850.
Kratzschmar, J., Krause, M., and Marahiel, M. A. (1989) Gramicidin-S biosynthesis operon containing the structural genes GRSA and GRSB has an open reading frame encoding a protein homologous to fatty-acid thioesterases. J. Bacteriol. 171, 5422–5429.
Sanchez-Quesada, J., Ghadiri, M. R., Bayley, H., and Braha, O. (2000) Cyclic peptides as molecular adapters for a pore-forming protein. J. Am. Chem. Soc. 122, 11,757–11,766.
Hirschmann, R., Yao, W. Q., Cascieri, M. A., et al. (1996) Synthesis of potent cyclic hexapeptide NK-1 antagonists. Use of a minilibrary in transforming a peptidal somatostatin receptor ligand into an NK-1 receptor ligand via a polyvalent peptidomimetic. J. Med. Chem. 39, 2441–2448.
Rohrer, S. P. and Schaeffer, J. M. (2000) Identification and characterization of subtype selective somatostatin receptor agonists. J. Physiol. Paris 94, 211–215.
Quartara, L., Pavone, V., Pedone, C., Lombardi, A., Renzetti, A. R., and Maggi, C. A. (1996) A review of the design, synthesis and biological activity of the bicyclic hexapeptide tachykinin NK2 antagonist MEN 10627. Regul. Pept. 65, 55–59.
Schiller, P. W., Berezowska, I., Nguyen, T. M.-D., et al. (2000) Novel ligands lacking a positive charge for the βand μ-opioid receptors. J. Med. Chem. 43, 551–559.
Boer, J., Gottschling, D., Schuster, A., Semmrich, M., Holzmann, B., and Kessler, H. (2001) Design and synthesis of potent and selective α4β7 integrin antagonists. J. Med. Chem. 44, 2586–2592.
Yoshida, M., Furumai, R., Nishiyama, M., Komatsu, Y., Nishino, N., and Horinouchi, S. (2001) Histone deacetylase as a new target for cancer chemotherapy. Cancer Chemother. Pharmacol. 48Suppl 1, S20–S26.
Yoshida, M., Horinouchi, S., and Beppu, T. (1995) Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays 17, 423–430.
Tkacz, J. S. and DiDomenico, B. (2001) Antifungals: what%s in the pipeline. Curr. Opin. Microbiol. 4, 540–545.
Okada, Y. (2001) Synthesis of peptides by solution methods. Curr. Org. Chem. 5, 1–43.
Lee, J. H., Griffin, J. H., and Nicas, T. I. (1996) Solid-phase total synthesis of bacitracin A. J. Org. Chem. 61, 3983–3986.
Kates, S. A., Sole, N. A., Johnson, C. R., Hudson, D., Barany, G., and Albericio, F. (1993) A novel, convenient, three-dimensional orthogonal strategy for solidphase synthesis of cyclic peptides. Tetrahedron Lett. 34, 1549–1552.
Tromelin, A., Fulachier, M.-H., Mourier, G., and Ménez, A. (1992) Solid-phase synthesis of a cyclic peptide derived from a curaremimetic toxin. Tetrahedron Lett. 33, 5197–5200.
Cabrele, C., Langer, M., and Beck-Sickinger, A. G. (1999) Amino acid side chain attachment approach and its application to the synthesis of tyrosine-containing cyclic peptides. J. Org. Chem. 64, 4353–4361.
Spatola, A. F., Crozet, Y., deWit, D., and Yanagisawa, M. (1996) Rediscovering an endothelin antagonist (BQ-123): A self-deconvoluting cyclic pentapeptide library. J. Med. Chem. 39, 3842–3846.
Rovero, P., Quartara, L., and Fabbri, G. (1991) Synthesis of cyclic-peptides on solid support. Tetrahedron Lett. 32, 2639–2642.
Spatola, A. F., Darlak, K., and Romanovskis, P. (1996) An approach to cyclic peptide libraries: reducing epimerization in medium sized rings during solid-phase synthesis. Tetrahedron Lett. 37, 591–594.
Trzeciak, A. and Bannwarth, W. (1992) Synthesis of head-to-tail” cyclised peptides on solid support by FMOC chemistry. Tetrahedron Lett. 33, 4557–4560.
McMurray, J. S. (1991) Solid-phase synthesis of a cyclic peptide using FMOC chemistry. Tetrahedron Lett. 32, 7679–7682.
McMurray, J. S., Lewis, C. A., and Obeyesekere, N. U. (1994) Influence of solid support, solvent and coupling reagent in the head-to-tail cyclisation of resin-bound peptides. Pept. Res. 7, 195–206.
Jensen, K. L., Alsina, J., Songster, M. F., Vagner, J., Albericio, F., and Barany, G. (1998) Backbone amide linker (BAL) strategy for solid-phase synthesis of Cterminal-modified and cyclic peptides. J. Am. Chem. Soc. 120, 5441–5452.
Bourne, G. T., Meutermans, W. D. F., Alewood, P. F., et al. (1999) A backbone linker for BOC-based peptide synthesis and on-resin cyclisation: synthesis of stylostatin 1. J. Org. Chem. 64, 3095–3101.
Gu, W. and Silverman, R. B. (2003) New stable backbone linker resins for solidphase peptide synthesis. Org. Lett. 5, 415–418.
Fridkin, M., Patchornik, A., and Katchalski, E. (1968) Use of polymers as chemical reagents II. Synthesis of bradykinin. J. Am. Chem. Soc. 90, 2953–2957.
Richter, L. S., Tom, J. Y. K., and Burnier, J. P. (1994) Peptide-cyclizations on solid support—a fast and efficient route to small cyclopeptides. Tetrahedron Lett.35, 5547–5550.
DeGrado, W. F. and Kaiser, E. T. (1982) Solid phase synthesis of protected peptides on a polymer bound oxime: preparation of segments comprising the sequence of a cytotoxic 26-peptide analog. J. Org. Chem. 47, 3258–3261.
DeGrado, W. F. and Kaiser, E. T. (1980) Polymer-bound oxime esters as supports for solid-phase peptide synthesis. The preparation of protected peptide fragments. J. Org. Chem. 45, 1295–1300.
Bourne, G. T., Golding, S. W., McGeary, R. P., et al. (2001) The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides. J. Org. Chem. 66, 7706–7713.
Nicolaou, K. C., Pfefferkorn, J. A., Mitchell, H. J., et al. (2000) Natural productlike combinatorial libraries based on privileged structures. 2. Construction of a 10,000-membered benzopyran library by directed split-and-pool chemistry using NanoKans and optical encoding. J. Am. Chem. Soc. 122, 9954–9967.
Gordon, E. M., Barrett, R. W., Dower, W. J., Fodor, S. P. A., and Gallop, M. A. (1994) Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. J. Med. Chem. 37, 1385–1401.
Gallop, M. A., Barrett, R. W., Dower, W. J., Fodor, S. P. A., and Gordon, E. M. (1994) Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J. Med. Chem. 37, 1233–1251.
Darwen, P. J., Bourne, G. T., Nielson, J., Tran, T. T., and Smythe, M. L. (2003) A gradient descent algorithm for minimizing the number of steps required for synthesis of cyclic-peptide libraries. Personal communication.
Hubener, G., Goehring, W., Musiol, H. J., and Moroder, L. (1992) N-α-trifluoroacetylation of N-terminal hydroxy amino acids: a new side reaction in peptide synthesis. Peptide Res. 5, 287–292.
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Bourne, G.T. et al. (2005). A Convenient Method for Synthesis of Cyclic Peptide Libraries. In: Howl, J. (eds) Peptide Synthesis and Applications. Methods in Molecular Biology™, vol 298. Humana Press. https://doi.org/10.1385/1-59259-877-3:151
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DOI: https://doi.org/10.1385/1-59259-877-3:151
Publisher Name: Humana Press
Print ISBN: 978-1-58829-317-6
Online ISBN: 978-1-59259-877-9
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