Skip to main content
SpringerLink
Log in

Synthesis and receptor binding of oxytocin analogs containing conformationally restricted amino acids

  • Published:
Letters in Peptide Science Aims and scope Submit manuscript

Abstract

We report the solid-phase synthesis and receptor-binding properties of eleven oxytocin analogs (Mpa-Xxx-Ile-Gln-Asn-Cys-Sar-Arg-Gly-NH2) containing non-coded amino acids in position 2: D-α- and L-α-(2-indanyl)glycine, R,S-6-methoxy-2-aminotetralin-2-carboxylic acid, D- and L-pentafluorophenylalanine, D,L-2,4-dimethylphenylalanine, D,L-2,4,6-trimethylphenylalanine, R,R- and S,S-1,2,3,4-tetrahydro-1-methyl-β-carboline-3-carboxylic acid and R- and S-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid. Some of these amino acid analogs (2-indanylglycine and D-pentafluorophenylalanine) were earlier successfully applied for the synthesis of potent bradykinin antagonists [1,2]. Their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The extent of binding of the peptides to the oxytocin receptor was in several cases was even higher than that of the parent hormone (oxytocin). However, the real pharmacological value of these analogs can be evaluated only after in vivo measurements of their inhibition of uterine motor activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Reissmann, S., Pineda, F., Vietinghoff, G., Werner, H., Gera, L., Stewart, J.M. and Paegelow, I., Peptides, 21 (2000) 527.

    Google Scholar 

  2. Gera, L. and Stewart, J.M., Immunopharm., 33 (1996) 174.

    Google Scholar 

  3. IUPAC-IUB Joint Commission on Biochemical Nomenclature, J. Biol. Chem., 219 (1984) 345.

    Google Scholar 

  4. du Vigneaud, V., Ressler, C., Swan, J.M., Roberts, C.W., Katsoyannis, P.G. and Gordon S., J. Am. Chem. Soc., 75 (1953) 4879.

    Google Scholar 

  5. du Vigneaud, V., Lawler, H.C. and Popenoe, E.A., J. Am. Chem. Soc., 75 (1953) 4880.

    Google Scholar 

  6. Goodwin, T.M., Valenzuela, G.J., Silver, H. and Creasy, G., Obstet. Gynecol., 88 (1996) 331.

    Google Scholar 

  7. The Worldwide Atosiban versus Beta-agonists Study Group, Br. J. Obstet. Gynecol., 108 (2001) 133.

    Google Scholar 

  8. Grzonka, Z., Kasprzykowsky, F., Darlak, K., Hahn, T.A. and Spatola, A.F., Peptide Res., 4 (1991) 270.

    Google Scholar 

  9. Grzonka, Z., Lammek, B., Kasprzykowsky, F., Gazis, D. and Schwartz, I.L., J. Med. Chem., 26 (1983) 555.

    Google Scholar 

  10. Lebl, M., Analogs with inhibitory properties. In: Jost, K., Lebl, M. and Brtnik, F. (Eds) Handbook of Neurohypophiseal Hormone Analogs Vol. 2. Boca Raton, CRC Press, 1987, pp. 17–74.

    Google Scholar 

  11. Hruby, V.J., Chan, W.Y., Rockway, T.W., Hlavacek, J. and Ormberg, J. In: Channa Basava and G.M. Anantharamaiah (Eds) Peptides: Design, Synthesis and Biological Activity Birkhauser, Boston, 1994, pp. 199–208.

    Google Scholar 

  12. Manning, M., Cheng, L.L., Stoev, S., Bankowski, K., Przybylski, J., Klis, W.A., Sawyer, W.H., Wo, N.C. and Chan, W.Y., J. Pept. Sci., 1 (1995) 66.

    Google Scholar 

  13. Manning, M., Nawrocka, E., Misicka, A., Olma, A., Klis, W.A., Seto, J. and Sawyer, W.H., J. Med. Chem., 27 (1984) 423.

    Google Scholar 

  14. Porter, T.H. and Shive, W., J. Med. Chem., 11 (1968) 402.

    Google Scholar 

  15. Hofmann, K., Finn, F.M. and Kiso, Y., J. Am. Chem. Soc., 100 (1978) 3585.

    Google Scholar 

  16. Herr, R.R., Enkoji, T. and Dailey, J.P., J. Am. Chem. Soc., 79 (1957) 4229.

    Google Scholar 

  17. Porter, J., Dykert, J. and Rivier, J., Int. J. Peptide Protein Res., 30 (1987) 13.

    Google Scholar 

  18. Darula, Zs., Kövér, K., Monory, K., Borsodi, A., Makó, É., Rónai, A., Tourwé, D., Péter, A. and Tóth, G., J. Med. Chem., 43 (2000) 1459.

    Google Scholar 

  19. Brossi, A., Focella, A. and Teitel, S., J.Med. Chem., 16 (1973) 418.

    Google Scholar 

  20. Moroder, L., Hallett, S., Wünsch, E., Keller, O. and Wersin, G., Hoppe Seyler's Z. Physiol. Chem., 357 (1976) 1651.

    Google Scholar 

  21. Merrifield, R.B., J. Am. Chem. Soc., 85 (1963) 2149.

    Google Scholar 

  22. Kaiser, E., Colescott, R. L., Bossinger, C.D. and Cook, P.J., Anal. Chem., 1987.

  23. Fuchs, A.R., Periyasami, S., Alexandrova, M. and Soloff, M.S., Endocrinology, 113 (1983) 742.

    Google Scholar 

  24. Marchingo, A.J.J., Abrahams, M., Woodcock, E.A., Smith, A.I., Mendelson, F.A.O. and Johnston, C.I., Endocrinology, 122/4 (1988) 1328.

    Google Scholar 

  25. Manning, M., Miteva, K., Pancheva, S., Stoev, S., Wo, N.C. and Chan, W.Y., Int. J. Pept. Prot. Res. 46 (1992) 244.

    Google Scholar 

  26. Manning, M., Lowbridge, J, Seto, J., Haldar, J. and Sawyer, W.H., J. Med. Chem., 21 (1978) 179.

    Google Scholar 

  27. Bankowski, K., Manning, M., Seto, J., Haldar, J. and Sawyer, W.H., Int. J. Pept. Prot. Res., 16 (1980) 382.

    Google Scholar 

  28. Tóth, G.K., Bakos, K., Penke, B., Pávó, I., Varga, Cs., Török, G., Péter, A. and Fülöp, F., Bioorg. Med. Chem. Lett., 9 (1999) 667.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary

    Krisztina Bakos

  2. Department of Pharmacy and Biopharmacy, University of Szeged, Eötvös u. 6, Szeged, Hungary

    Judit Havass & George Falkay

  3. Department of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, Szeged, Hungary

    Ferenc Fülöp

  4. Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, U.S.A

    Lajos Gera & John M. Stewart

  5. Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary

    Gábor K. Tóth

Authors
  1. Krisztina Bakos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Judit Havass
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ferenc Fülöp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lajos Gera
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John M. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. George Falkay
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gábor K. Tóth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gábor K. Tóth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bakos, K., Havass, J., Fülöp, F. et al. Synthesis and receptor binding of oxytocin analogs containing conformationally restricted amino acids. Letters in Peptide Science 8, 35–40 (2001). https://doi.org/10.1023/A:1014242727915

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1014242727915

Search

Navigation