New Analogues of Bradykinin Substituted in the C-Terminal Part of the Molecule with Naphthylalanine

• Autorzy: Prahl A. , Derdowska I. , Dawidowska O. , Neubert K. , Hartrodt B. , Wierzba T. , Juzwa W. , Lammek B.
• Języki publikacji: EN

Abstrakty

EN

This paper describes the synthesis and some pharmacological properties of eight new analogues of a previously synthesized bradykinin antagonist, D-Arg-Arg-Pro-Hyp-Gly- Thi-Ser-D-Phe-Thi-Arg. Two peptides were designed by substitution of Thi8 with L-1- and L-2-naphthylalanine. In two further analogues this modification was combined with placement in position 7 of D-2-naphthylalanine residue. Finally, we obtained four analogues by acylation of N-terminus of the peptides mentioned above with 1-adamantaneacetic acid. The activity of analogues was assessed by their ability to inhibit vasodepressor response to exogenous bradykinin (rat blood pressure test). Our results indicate that the modification proposed decreased the B2 antagonistic activity, however, the range of this effect was different. We also observed that even minor changes in the structure of the C-terminal part of the B2 antagonists may significantly influence their activity.

Słowa kluczowe

EN

rat uterus assay; bradykinin; B2-antagonists

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2002
• Tom: Vol. 76 / nr 10
• Strony: 1433--1439
• Opis fizyczny: Bibliogr. 12 poz., rys.

Twórcy

autor

Prahl A.

• Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdańsk, Poland

autor

Derdowska I.

• Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdańsk, Poland

autor

Dawidowska O.

• Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdańsk, Poland

autor

Neubert K.

• Institute of Biochemistry, Martin-Luther- University Halle- Wittenberg Kurt-Mothes-Strafie 3, 06120 Halle (Saale), Germany

autor

Hartrodt B.

• Institute of Biochemistry, Martin-Luther- University Halle- Wittenberg Kurt-Mothes-Strafie 3, 06120 Halle (Saale), Germany

autor

Wierzba T.

• Department of Physiology, Medical Academy of Gdansk, Dębinki 1, 80-211 Gdansk, Poland

autor

Juzwa W.

• Department of Physiology, Medical Academy of Gdansk, Dębinki 1, 80-211 Gdansk, Poland

autor

Lammek B.

• Department of Physiology, Medical Academy of Gdansk, Dębinki 1, 80-211 Gdansk, Poland

Bibliografia

• 1. Farmer S.G. and Burch R.M., The Pharmacology of Bradykinin Receptors. In: Burch R.M. (ed.), Bradykinin Antagonists. Basic and Clinical Research. Marcel Dekker Inc., NY-Basel-Hong Kong 1991, pp 1-31.
• 2. Hock F.J., Wirth K., Albus U., Linz W., Gerhards H. J,, Wiemer G., Henke St., Breipohl G., König W., Knolle J. and Scholkens B.A., Br. J. Pharmacol, 102, 769 (1991).
• 3. Stewart J.M., Gera L., Hanson W., Juzack J., Burkard M., Me Cullough R. and Whalley E.T., Immunopharmacology, 33, 51 (1966).
• 4. Lammek B., Wang Y.X., Gavras I. and Gavras H., Peptides, 11, 1041 (1990).
• 5. Lammek B., Wang Y.X., Gavras I. and Gavras H., J Pharm. Pharmacol., 43, 887 (1991).
• 6. Lammek B., Polish J. Chem., 68, 913 (1994).
• 7. Prahl A., Wierzba T., Winklewski P., Wszędybył M., Cherek M., Juzwa W. and Lammek B,, Collect. Czech. Chem. Commun., 62, 1940 (1997).
• 8. Stewart J.M. and Vavrek R.J., In: Burch R.M. (ed.), Bradykinin Antagonists. Basic and Clinical Research. Marcel Dekker Inc., NY-Basel-Hong Kong 1991, pp 51-96.
• 9. Schächter L.R, Uchida Y., Longridge D.J., Łabędź T., Whatley F.T., Vavrek R.J. and Stewart J.M., Br J. Pharmacol, 92, 851 (1987),
• 10. Wang S.S., J. Am. Chem. Soc., 95, 1328 (1973).
• 11. Manning M. and Sawyer W.H., Development of Selective Agonists and Antagonists of Vasopressin and Oxytocin. In: Schrier R.W. (ed.), Vasopressin. Raven Press, NY 1985, pp 131-144.
• 12. Tallarida R.J. and Murray R.B., Manual of Pharmacologic Calculations, Springer Verlag, Berlin-Heidelberg-NY 1987.