Abstract
Poor oral bioavailability, low metabolic stability towards proteolysis and rapid excretion via both liver and kidneys displayed by innumerable peptides of potential therapeutic value has generated an intensive search for peptidomimics (1–2). A possible approach of such nonpeptidal peptidomimics is to replace the peptide by a scaffold that distributes in the space the peptidal side chains of amino acids essential for biological activity and mimics the bioactive conformation of the peptide.
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
Holzemann, G. (1991) Peptide conformation mimetics. Kontakte (Darmstadt) 3–12 and 55–63.
Giannis, A. and Kolter, T. (1993) Peptidomimetics for receptor ligands-discovery, development, and medical perspectives. Angew. Chem. Int. Ed. Engl. 32, 1244–1267.
Belanger, P. C. and Dufresne, C. (1986) Preparation of exo-6-benzyl-exo-2-(m-hydroxyphenyl)-l-dimethylaminobicyclo[2.2.2]octane. A non-peptide mimic of enkephalins. Can. J. Chem. 64, 1514–1520.
Hirschmann, R., Sprengeler, P. A., Kawasaki, T., Leahy, J. W., Shakespeare, W. C, and Smith, A. B., III (1993) The versatile steroid nucleus: design and synthesis of a peptidomimetic employing this novel scaffold. Tetrahedron 49, 3665–3676.
Hirschmann, R., Nicolaou, K. C, Pietranico, S., Salvino, J., Leahy, E. M., Sprengeler, P. A., Furst, G., Smith, A.B., III, Strader, C. D., Cascieri, M. A., Candelore, M. R., Donaldson, C., Vale, W., and Maechler, L. (1992) Nonpeptidal peptidomimetics with a β-d-glucose scaffolding. A partial Somatostatin agonist bearing a close structural relationship to a potent, selective substance P antagonist. J. Am. Chem. Soc. 114, 9217–9218.
Hirschmann, R., Nicolaou, K. C., Pietranico, S., Leahy, E. M., Salvino, J., Arison, B., Cichy, M. A., Spoors, P. G., Shakespeare, W.C., Sprengeler, P.A., Hamley, P., Smith, A. B., III, Reisine, T., Raynor, K., Maechler, L., Donaldson, C, Vale, W., Freidinger, R. M., Cascieri, M. R., and Strader C. D. (1993) De novo design and synthesis of Somatostatin non-peptide peptidomimetics utilizing β-d-glucose as a novel scaffolding. J. Am. Chem. Soc. 115, 12,550–12,568.
Le Diguarher, T., Boudon, A., Elwell, C, Paterson, D. E., and Billington, D. C. (1996) Synthesis of potential peptidomimetics based on highly substituted glucose and allose scaffolds. Biorg. Med. Chem. Lett. 6, 1983–1988.
Papageorgiou, C, Haltiner, R., Bruns, C, and Petcher, T. J. (1992) Design, synthesis, and binding affinity of a nonpeptide mimic of somatostatin. Bioorg. Med. Chem. Lett. 2, 135–140.
Papageorgiou, C. and Borer, X. (1996) A non-peptide ligand for the somatostatin receptor having a benzodiazepine structure. Bioorg. Med. Chem. Lett. 6, 267–272.
Le Merrer, Y., Poitout, L., Depezay, J.-C, Dosbaa, I., Geoffroy, S., and Foglietti, M.-J. (1997) Synthesis of azasugars as potent inhibitors of glycosidases. Bioorg. Med. Chem. 5, 519–533.
Damour, D., Barreau, M., Blanchard, J.-C, Burgevin, M.-C, Doble, A., Herman, F., Pantel, G., James-Surcouf, E., Vuilhorgne, M., Mignani, S., Poitout, L., Le Merrer, Y., and Depezay, J.-C. (1996) Design, synthesis and binding affinities of novel non-peptide mimics of Somatostatin/Sandostatin®. Bioorg. Med. Chem. Lett. 6, 1667–1672.
Damour, D., Depezay, J.-C, Le Merrer, Y., Mignani, S., Pantel, G., and Poitout, L. (1995) Dérivés de la tryptamine, leur préparation et les médicaments les contenant French Patent application # 95 05510.
Lamberts, S. W. J., Krenning, E. P., and Reubi, J.-C. (1991) The role of somatostatin and its analogs in the diagnosis and treatment of tumors. Endocrine Rev. 12, 450–482.
Hoyer, D., Bell, G. I., Berelowitz, M., Epelbaum, J., Feniuk, W., Humphrey, P. P. A., O’Caroll, A.-M., Patel, Y. C, Schonbrunn, A., Taylor, J. E., and Reisine, T. (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol. Sci. 16, 86–88.
Huang, Z., He Yα-Bo, Raynor, K., Tallent, M., Reisine, T., and Goodman, M. (1992) Main chain and side chain chiral methylated somatostatin analogs: synthesis and conformational analyses. J. Am. Chem. Soc. 114, 9390–9400.
Moreau, J. P. and DeFeudis, F. V. (1987) Pharmacological studies of somatostatin and somatostatin-analogs: therapeutic advances and perspectives. Life Sci. 40, 419–437.
Hocart, S. J., Reddy, V., Murphy, W. A. and Coy, D. H. (1995) Three-dimensional quantitative structure-activty relationships of somatostatin analogs. 1. Comparative molecular field analysis of growth hormone release-inhibiting potencies. J. Med. Chem. 38, 1974–1989.
Wolf, H. (1947) Reactions and generation of hydrazoic acid. Org. React. 3, 8–45.
Hughes, D. L. (1992) The Mitsunobu reaction. Org. React. 42, 335–656.
Jurczak, J., Bauer, T., and Chmielewski, M. (1987) A general approach to the synthesis of 2,3-di-O-protected derivatives of d-glyceraldehyde. Carbohydr. Res. 164, 493–498.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Le Merrer, Y., Poitout, L., Depezay, JC. (1999). Synthesis of Peptidomimics Through Sugar-Based Scaffolds. In: Kazmierski, W.M. (eds) Peptidomimetics Protocols. Methods in Molecular Medicine™, vol 23. Humana Press. https://doi.org/10.1385/0-89603-517-4:227
Download citation
DOI: https://doi.org/10.1385/0-89603-517-4:227
Publisher Name: Humana Press
Print ISBN: 978-0-89603-517-1
Online ISBN: 978-1-59259-605-8
eBook Packages: Springer Protocols