New bradykinin B2 receptor antagonists - influence of C-terminal segment modifications on their pharmacological properties

• Autorzy: Sleszynska M. , Kwiatkowska A. , Sobolewski D. , Wierzba T.H. , Katarzynska J. , Zabrocki J. , Borovickova L. , Slaninova J. , Prahl A.
• Języki publikacji: EN

Abstrakty

EN

In the present study we describe the synthesis and some pharmacological properties of eight new analogues of bradykinin (BK). Two peptides were designed by substitution of position 7 or 8 of the known [d-Arg0,Hyp3,Thi5,8,d-Phe7]BK antagonist (Stewart's antagonist) with l-pipecolic acid (l-Pip). The next two analogues were obtained by replacement of the d-Phe residue in position 7 of the Stewart's peptide with l-β2-isoproline (l-β2-iPro) or l-β3-homoproline (l-β3-hPro). The four analogues mentioned above were also prepared in N-acylated form with 1-adamantaneacetic acid (Aaa). Biological activity of the compounds was assessed by isolated rat uterus and rat blood pressure tests. Our results showed that l-Pip in position 7 slightly increased antagonistic potency in the blood pressure test, but it turned the analogue into an agonist in the rat uterus test. Replacement of Thi by l-Pip in position 8 also enhanced antagonism in the rat pressure test but preserved the antagonism in the rat uterus test. l-β2-iPro or l-β3-hPro in position 7 decreased the potencies in both tests. We also demonstrated that acylation of the N-terminus did not increase, as was claimed previously, the antagonistic potencies of the resulting peptides. The results thus support the hypothesis about the existence of different types of BK receptors in the rat uterus and blood vessels. Our studies provide new information about the structure-activity relationship of BK antagonists which may help in designing more potent BK receptor blockers.

Słowa kluczowe

EN

pharmacological property; bradykinin analogue; blood pressure test; uterotonic test; sterically restricted residue; bradykinin B2 receptor antagonist; rat; new bradykinin

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2009
• Tom: 56
• Numer: 4
• Strony: 641-648
• Opis fizyczny: p.641-648,fig.,ref.

Twórcy

autor

Sleszynska M.

• University of Gdansk, J.Sobieskiego 18/19, 80-952 Gdansk, Poland

autor

Kwiatkowska A.

autor

Sobolewski D.

autor

Wierzba T.H.

autor

Katarzynska J.

autor

Zabrocki J.

autor

Borovickova L.

autor

Slaninova J.

autor

Prahl A.

Bibliografia

• Ahluwalia A, Perretti M (1999) B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci 20: 100-104. 
• Akbary A, Wirth KJ, Schölkens BA (1996) Efficacy and tolerability of icatibant (Hoe 140) in patients with moderately severe chronic bronchial asthma. Immunopharmacology 33: 238-242. 
• Boels K, Schaller HC (2003) Identification and characterization of GPR100 as a novel human G-protein-coupled bradykinin receptor. Br J Pharmacol 140: 932-938. 
• Borkowski JA, Ransom RW, Seabrook GR, Trumbauer M, Chen H, Hill RG, Strader CD, Hess JF (1995) Targeted disruption of a B2 bradykinin receptor gene in mice eliminates bradykinin action in smooth muscle and neurons J Biol Chem 270: 13706-13710. 
• Cardillo G, Gentilucci L, Melchiorre P, Spampinato S (2000) Synthesis and binding activity of endomorphin-1 analogues containing β-amino acids. Bioorg Med Chem Lett 10: 2755-2758. 
• Cardillo G, Gentilucci L, Qasem AR, Sgarzi F, Spampinato S (2002) Endomorphin-1 analogues containing β-proline are μ-opioid receptor agonists and display enhance enzymatic hydrolysis resistance. J Med Chem 45: 2571-2578.  
• Couture R, Harrisson M, Vianna RM, Cloutier F (2001) Kinin receptors in pain and inflammation. Eur J Pharmacol 429: 161-176. 
• Derdowska I, Prahl A, Neubert K, Hartrodt B, Kania A, Dobrowolski D, Melhem S, Trzeciak HI, Wierzba T, Lammek B (2001) New analogues of bradykinin containing a conformationally restricted dipeptide fragment in their molecules. J Pept Res 57: 11-18. 
• Farmer SG, Burch RM, Meeker SA, Wilkins DE (1989) Evidence for a pulmonary B3 bradykinin receptor. Mol Pharmacol 36: 1-8. 
• Fein AM, Bernard GR, Criner GJ, Fletcher EC, Good JT Jr, Knaus WA, Levy H, Matuschak GM, Shanies HM, Taylor RW (1997) Treatment of severe systemic inflammatory response syndrome and sepsis with a novel bradykinin antagonist, deltibant (CP-0127). Results of a randomized, double-blind, placebo-controlled trial. CP-0127 SIRS and Sepsis Study Group. J Am Med Assoc 277: 482-487. 
• Fink MP (1998) Therapeutic options directed against platelet activating factor, eicosanoids and bradykinin in sepsis. J Antimicrob Chemother 41: 81-94. 
• Fujie H, Hayashi I, Oh-ishi S (1993) The kinin released from high molecular weight-kininogen is responsible for inflammatory exudation in rats: detection of kinin-free-kininogen in the exudates by immunoblot analysis. Life Sci 53: 1691-1701. 
• Hall JM, Morton IKM (1997) Immunopharmacology of bradykinin receptors. In The Kinin System. Farmer SG, Handbook of Immunopharmacology. The Academic Press, London.
• Heitsch H (2003) The therapeutic potential of bradykinin B2 receptor agonists in the treatment of cardiovascular disease. Expert Opin Investig Drugs 12: 759-770. 
• Hock FJ, Wirth K, Albus U, Linz W, Gerhards HJ, Wiemer G, Henke S, Breipohl G, König W, Knolle J (1991) Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol 102: 769-773. 
• Holton P (1948) A modification of the method of Dale and Lindlow for standardization of posterior pituitary extract. Br J Pharmacol 3: 328-334.
• Howl J, Payne SJ (2003) Bradykinin receptors as a therapeutic target. Expert Opin Ther Targets 7: 277-285. 
• Klein SI, Czekaj M, Molino BF, Chu V (1997) Constrained β-alanine based GpIIb/IIIa antagonists. Bioorg Med Chem Lett 7: 1773-1778.
• Labudda-Dawidowska O, Wierzba TH, Prahl A, Kowalczyk W, Gawiński Ł, Plackova M, Slaninová J, Lammek B (2005) New bradykinin analogues modified in the C-terminal part with sterically restricted 1-aminocyclohexane-1-carboxylic Acid. J Med Chem 48: 8055-8059. 
• Labudda O, Wierzba T, Sobolewski D, Kowalczyk W, Śleszyńska M, Gawiński Ł, Plackova M, Slaninová J, Prahl A (2006) New bradykinin analogues substituted in positions 7 and 8 with sterically restricted 1-aminocyclopentane-1-carboxylic acid. J Pept Sci 12: 775-779. 
• Labudda O, Wierzba T, Sobolewski D, Śleszyńska M, Gawiński Ł, Plackova M, Slaninová J, Prahl A (2007) New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure. Acta Biochim Polon 54: 193-197. 
• Lammek B (1994) Design and synthesis of B2-antagonists of bradykinin. Pol J Chem 68: 913-920.
• Lammek B, Wang YX, Gavras I, Gavras H (1990) A new highly potent antagonist of bradykinin. Peptides 11: 1041-1043. 
• Lammek B, Wang YX, Gavras I, Gavras H (1991) A novel bradykinin antagonist with improved properties. J Pharm Pharmacol 43: 887-888. 
• Marceau F, Regoli D (2004) Bradykinin receptor ligands: therapeutic perspectives. Nat Rev Drug Discov 3: 845-852. 
• McLean PG, Perretti M, Ahluwalia A (2000) Kinin B1 receptors as novel anti-inflammatory targets. Emerg Ther Targets 4: 127-141.
• Munsick R (1960) Effect of magnesium ion on the response of the rat uterus to neurohypophysial hormones and analogues. Endocrinology 6: 451-457. 
• Odya C, Goodfriend T, Pena C (1980) Bradykinin receptor-like binding studied with iodinated analogues. Biochem Pharmacol 29: 175-185. 
• Perkins MN, Campbell E, Dray A (1993) Antinociceptive activity of the bradykinin B1 and B2 receptor antagonists, des-Arg9[Leu8]-BK and Hoe 140, in two models of persistent hyperalgesia in the rat. Pain 53: 191-197. 
• Plevin R, Owen P (1988) Multiple B2 kinin receptors in mammalian tissues. Trends Pharmacol Sci 9: 387-389. 
• Prahl A, Derdowska I, Dawidowska O, Neubert K, Hartrodt B, Wierzba T, Juzwa W, Lammek B (2003) New bradykinin analogues substituted in positions 6 and 7 with naphthylalanine. Pol J Chem 77: 881-887.
• Prahl A, Wierzba T, Winklewski P, Musiał P, Juzwa W, Lammek B (1997a) Antagonists of bradykinin modified with conformationally restricted dipeptide fragment. Pol J Chem 71: 929-935.
• Prahl A, Wierzba T, Winklewski P, Wszędybył M, Cherek M, Juzwa W, Lammek B (1997b) Influence of C-terminal modifications of bradykinin antagonists on their activity. Collect Czech Chem Commun 62: 1940-1946.
• Proud D, Bathon JM, Togias AG, Naclerio RM (1995) Inhibition of the response to nasal provocation with bradykinin by HOE-140: efficacy and duration of action. Can J Physiol Pharmacol 73: 820-826. 
• Regoli D, Gobeil F, Nguyen QT, Jukic D, Seoane PR, Salvino JM, Sawutz DG (1994) Bradykinin receptor types and B2 subtypes. Life Sci 55: 735- 749. 
• Schachter LR, Uchida Y, Londridge DJ, Łabędź T, Whalley ET, Vavrek RJ, Stewart JM (1987) New synthetic antagonists of bradykinin. Br J Pharmacol 92: 851-855. 
• Sharma JN (1993) Therapeutic prospects of bradykinin receptor antagonists. Gen Pharmacol 24: 267-274. 
• Sikorska E, Rodziewicz-Motowidło S (2008) Solution conformations of bradykinin antagonists modified with Cα-Cα cyclized nonaromatic residues. J Pept Sci 14: 819-829. 
• Steranka L, Manning D, Dehas C, Ferkany J, Borosky S, Connor J, Vavrek R, Stewart J, Shyder J (1988) Bradykinin as a pain mediator: Receptors are localized to sensory neurons and antagonists have analgesic actions. Proc Natl Acad Sci USA 85: 3245-3249. 
• Stewart JM, Gera L, York EJ, Chan DC, Bunn PA Jr (1999) Bradykinin antagonists: present progress and future prospects. Immunopharmacology 43: 155-161. 
• Toniolo C, Crisma M, Valle G, Bonora GM, Polinelli S, Becker EL, Freer RJ, Sudhanand R, Rao RB, Balaram B, Sukumar M (1989) Conformationally restricted formyl methionyl tripeptide chemoattractants: a three-dimensional structure-activity study of analogs incorporating a C alpha, alpha-dialkylated glycine at position 2. Pept Res 2: 275-281. 
• Toniolo C, Benedetti E (1994) Structures of polypeptides from α-amino acids disubstituted at the α-carbon. Macromolecules 24: 4004-4009.
• Paul PKC, Sukumar M, Bardi R, Piazzesi AM, Valle G, Toniolo C, Balaram P (1986) Stereochemically constrained peptides. Theoretical and experimental studies on the conformations of peptides containing 1-aminocyclohexanecarboxylic acid. J Am Chem Soc 108: 6363-6370.
• Paradisi M, Torrini I, Zecchini GP, Luente G, Gauvuzzo E, Mazza F, Pochetti G (1995) γ-Turn conformation induced by α,α-disubstituted amino acids with a cyclic six-membered side chain. Tetrahedron 51: 2379-2386.
• Trifilieff A, Amrani Y, Landry Y, Gies JP (1993) Comparative action of new highly potent bradykinin receptor antagonists in the guinea-pig trachea. Eur J Pharmacol 239: 227-229. 
• Turner P, Dear J, Scadding G, Foreman JC (2001) Role of kinins in seasonal allergic rhinitis: icatibant, a bradykinin B2 receptor antagonist, abolishes the hyperresponsiveness and nasal eosinophilia induced by antigen. J Allergy Clin Immunol 107: 105-113. 
• Vavrek RJ, Stewart JM (1985) Competitive antagonists of bradykinin. Peptides 6: 161-164. 
• Wang SS (1973) p-Alkoxybenzyl alcohol resin and p-alkoxybenzyloxycarbonyl hydrazide resin for solid phase synthesis of protected peptide fragments. J Am Chem Soc 95: 1328-1333. 
• Whalley ET, Clegg S, Stewart JM, Vavrek RJ (1987) The effect of kinin agonists and antagonists on the pain response of human blister base. Naunyn-Schmiedeberg's Arch Pharmacol 336: 652-655. 
• Zausinger S (2003) Bradykinin receptor antagonists in cerebral ischemia and trauma. IDrugs 6: 970-975.