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The 1,5-Disubstituted Tetrazole Ring as a cis-Amide Bond Surrogate

  • Janusz Zabrocki
  • Garland R. Marshall
Part of the Methods in Molecular Medicine™ book series (MIMM, volume 23)

Abstract

Proline occupies a special role among those amino acids incorporated into peptides and proteins by the normal ribosomal pathways, since it is the only residue that leads to an N-alkyl amide bond. In peptide natural products that often have special biosynthetic pathways or unusual posttranslational modifications, N-methyl amino acids are common and may play a special role because of their conformational properties, including their proclivity for cis-trans isomerism of the amide bond. Numerous peptides with important biological activities, such as cyclosporin and didemnin, contain N-methyl amino acids. Cis-trans isomerism of the N-alkyl amide bond involving the amino group can readily be observed (1) in the NMR of proline and N-methyl amino acid-containing peptides. In the case of angiotensin and thyroliberin (TRH) analogs, the quantity of cis-isomer in aqueous solution was correlated (2) with the biological activity. This suggested that the cis-isomer might be the one bound to the receptor and responsible for the observed biological activity. Bairaktari et al. (3) have reported that the normal amide bond between an He and Lys residues in the linear peptide, bombolitin, has the cis-conformation when bound to phospholipid micelles. In protei0n crystal structures, cis-amide bond conformations are occasionally observed for the normal, nonalkylated amide bond. A cis-amide bond predisposes the peptide for a reverse turn, a so-called Type VI β-turn. Brandl and Deber (4) have proposed that cis-trans isomerism of proline residue might play a role in transduction of transmembrane proteins.

Keywords

Amide Bond Flash Chromatography Hydrogen Fluoride Benzyl Ester Tetrazole Ring 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Thomas, W. A. and Williams, M. K. (1972) 13C Nuclear magnetic resonance spectroscopy and cis/trans isomerism in dipeptides containing proline. J. Chem. Soc., Chem. Commun. 994.Google Scholar
  2. 2.
    Liakopoulou-Kyriakides, M. and Galardy, R. E. (1979) s-Cis and s-Trans isomerism of the his-pro peptide bond in angiotensin and thyroliberin analogues. Biochemistry 18, 1952–1957.CrossRefGoogle Scholar
  3. 3.
    Bairaktari, E., Mierke, D. F., Mammi, S., and Peggion, E. J. (1990) Observation of a cis amide isomer within a linear peptide. J. Am. Chem. Soc. 112, 5383.CrossRefGoogle Scholar
  4. 4.
    Brandl, C. J. and Deber, C. M. (1986) Hypothesis about the function of membrane-buried proline residues in transport proteins. Proc. Natl. Acad. Sci. USA 83, 917–921.CrossRefGoogle Scholar
  5. 5.
    Hann, M. M., Sammes, P. G., Kennewell, P. D., and Taylor, J. B. (1982) On double bond isosteres of the peptide bond; an enkephalin snalog. J. Chem Soc., Perkin Trans. 1, 307–314.CrossRefGoogle Scholar
  6. 6.
    Marshall, G. R., Humblet, C, Van Opdenbosch, N., and Zabrocki, J. (1981) Peptide bond modification and its effect on conformational mimicry, in Peptides: Synthesis-Structure-Function, Proceedings of the Seventh American Peptide Symposium (Rich D. H. and Gross E., eds.), Pierce Chemical, Rockford, IL, pp. 669–672.Google Scholar
  7. 7.
    Zabrocki, J., Smith, D. G., Dunbar, J. B., Jr., Iljima, H., and Marshall G. R. (1988) Conformational mimicry. 1. 1,5-Disubstituted tetrazole ring as a surrogate for the cis amide bond. J. Am. Chem. Soc. 110, 5875–5880.CrossRefGoogle Scholar
  8. 8.
    Smith, G. D., Zabrocki, J., Flak, T. A., and Marshall G. R. (1991) Conformational mimicry: II. An obligatory cis amide bond in a small linear peptide. Int. J. Pept. Protein Res. 37, 191–197.CrossRefGoogle Scholar
  9. 9.
    Yu, K-L. and Johnson, R. L. (1987) Synthesis and chemical properties of tetrazole peptide analogs. J. Org. Chem. 52, 2051–2059.CrossRefGoogle Scholar
  10. 10.
    Hirai, K., Iwano, Y., Saito, T., Hiraoka, T., and Kishida, Y. (1976) Functionalization of C6(7) of penacillamins and cephalosporins via 1,3-dipolar intermediate. Tetrahedron Lett. 16, 1303–1306.CrossRefGoogle Scholar
  11. 11.
    Zabrocki, J., Dunbar, J. B., Jr., Marshall, K. W., Toth, M. V., and Marshall, G. R. (1992) Conformational mimicry. Part HI. Synthesis and incorporation of 1,5-disubstituted tetrazole dipeptide analogs into peptides with preservation of chiral integrity: bradykinin. J. Org. Chem. 57, 202–209.CrossRefGoogle Scholar
  12. 12.
    Zabrocki, J. and Marshall, G. R., work in progress.Google Scholar
  13. 13.
    Veber, D. F., Saperstein, R., Nutt, R. F., Freidinger, R. M., Brady, S. F., Curley, P., et al. (1984) A Super active cyclic hexapeptide analog of somatostatin. Life Sci. 34, 1371–1378.CrossRefGoogle Scholar
  14. 14.
    Beusen, D. D., Zabrocki, J., Slomczynska, U., Head, R. D., Kao, J., and Marshall, G. R. (1995) Conformational mimicry: synthesis and solution conformation of a cyclic somatostatin hexapeptide containing a tetrazole cis-amide bond surrogate. Biopolymers 36, 181–200.CrossRefGoogle Scholar
  15. 15.
    Zabrocki, J., Smith, G. D., Dunbar, J. B., Jr., Marshall, K. W., Toth, M., and Marshall, G. R. Tetrazole peptide analogs, in Peptides 1988, Proceedings of the 20th European Peptide Symposium (Jung G. and Bayer E., eds.), Walter de Gruyter, Berlin, pp. 295–297.Google Scholar
  16. 16.
    Zabrocki J. and Olejniczak B. (1993) Tetrazole analogs of Leu-enkephalin. 12th Polish Peptide Symposium, Karpacz, Poland, Abstract, p. 98.Google Scholar
  17. 17.
    Zabrocki J., Olczak J., Kaczmarek K., Maszczynska I., and Lipkowski A. W. (1995) The synthesis of tetrazole analogs of dipeptides containing glycine in N-terminal position. Leu-enkephalin analogs. 13th Polish Peptide Symposium, Gdansk, Poland, Abstract, p. 40.Google Scholar
  18. 18.
    Boteju, L. W. and Hruby, V. J. (1993) Tryptophan-containing 1,5-tetrazole dipeptide analogs: synthesis of Trp Ψ[CN4]Nle as a cis amide bond surrogate. Tetrahedron Lett. 34, 1757–1760.CrossRefGoogle Scholar
  19. 19.
    Boteju, L. W., Zalewska, T., Yamamura, H. I., and Hruby, V. J. (1993) Tryptophan-norleucine 1,5-disubstituted tetrazoles as cis peptide bond mimics: investigation of the bioactive conformation of a potent and selective peptide for the cholecystokinin-B receptor. Bioorg. Med. Chem. Lett. 3, 2011–2016.CrossRefGoogle Scholar
  20. 20.
    Lebl, M., Slaninova, J., and Johnson, R. L. (1990) Analogs of oxytocin containing a pseudopeptide Leu-Gly bond of cis and trans configuration. Int. J. Pept. Protein Res., 33, 16–21.CrossRefGoogle Scholar
  21. 21.
    Valle, G., Crisma, M., Yu, K.-L., Toniolo, C, Mishra, R. K., and Johnson, R. L. (1988) Synthesis and X-ray diffraction analysis of the tetrazole peptide analogue Pro-Leu-Ψ[CN4]-Gly-NH2. Coll. Czech. Chem. Commun. 53, 2863–2876.CrossRefGoogle Scholar
  22. 22.
    Marshall, G. R., Vine, W. H., and Needleman, P. (1970) A specific competitive inhibitor of angiotensin II. Proc. Natl. Acad. Sci. USA 67, 1624–1630.CrossRefGoogle Scholar
  23. 23.
    von Braun, J. (1931) Untersuchungen uber die Bestandteile des Erdols. Ann., 490, 100–179.Google Scholar
  24. 24.
    Stewart, J. M. and Young, J. D. (1984) Solid Phase Peptide Synthesis. Pierce Chemical Co., Rockford, IL.Google Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1999

Authors and Affiliations

  • Janusz Zabrocki
    • 1
  • Garland R. Marshall
    • 1
  1. 1.Department of Molecular Biology and Pharmacology, Center for Molecular DesignWashington UniversitySt. Louis

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