New Bradykinin Analogues Modified in Position 6 and 7 with Naphthylalanine

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

Abstrakty

EN

We describe 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 Ser6 with L-1- and L-2-naphthylalanine. In two further analogues this modification was combined with placement in position 7 of D-naphthylalanine residue. We also 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 modifications proposed decreased significantly the B2 antagonistic activity. Moreover, our earlier observation, suggesting that acylation of the N-terminus of many BK antagonists with bulky groups consistently improved the antagonistic potency, appears to be valid only for one pair of analogues.

Słowa kluczowe

EN

bradykinin; B2-antagonists; rat blood pressure assay

• Wydawca: Polskie Towarzystwo Chemiczne
• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2003
• Tom: Vol. 77 / nr 7
• Strony: 881--887
• Opis fizyczny: Bibliogr. 10 poz., rys.

Twórcy

autor

Prahl A.

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

autor

Derdowska I.

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

autor

Dawidowska O.

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

autor

Neubert K.

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

autor

Hartrodt B.

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

autor

Wierzba T.

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

autor

Juzwa W.

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

autor

Lammek B.

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

Bibliografia

• 1. Farmer S.G. and Burch R.M., in; Bradykinin Antagonists. Basic and Clinical Research. R.M. Burch (Ed.), Marcel Dekker Inc., NY-Basel (1991), pp. 1-31.
• 2. Stewart J.M. and Vavrek R.J., Chemistry of peptide B2 bradykinin antagonist. In: Bradykinin Antagonists. Basic and Clinical Research. R.M. Burch (Ed.), Marcel Dekker Inc., NY-Basel (1991), pp. 51-96.
• 3. Prahl A., Wierzba T., Winklewski P., Wszqdybyi M., Cherck M., Juzwa W. and Lammek B., Collect. Czech. Chem. Commun., 62, 1940(1997).
• 4. Prahl A., Derdowska I., Dawidowska O., Neubert K.., Hartrodt B., Wierzba T., Juzwa W. and Lammek B„ Polish J. Chem., 76, 1437 (2002).
• 5. Prahl A., Wierzba T., Winklewski P., Musial P., Juzwa W. and Lammek B., Polish J. Chem., 71, 929 (1997).
• 6. Manning M. and Sawyer W.H., Development of Selective Agonist and Antagonist of Vasopressin and Oxytocin. In: Schrier R.W. (ed.), Vasopressin. Raven Press, NY 1985, pp. 131-144.
• 7. Tallarida R.J. and Murray R.B., Manual of Pharmacological Calculations, Springer Verlag, Berlin-Heidelberg-NY, 1987.
• 8. Lammek B., Wang Y.X., Gavras I. and Gavras H., Peptides, 11, 1041 (1990).
• 9. Lammek B., Kazmierkiewicz R., Ito Y. and Gavras H., Polish J. Chem.. 67, 1053(1993).
• 10. Schachter L.R., Uchida Y., Longridge D.J, Labqdz T., Whalley F.T., Vavrek R.J. and Stewart J.M., Br. J. Pharmacol, 92, 851 (1987).