New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure

• Authors: Olga Labudda , Tomasz Wierzba , Dariusz Sobolewski , Małgorzata Śleszyńska , Łukasz Gawiński , Marketa Plackova , Jiřina Slaninová , Adam Prahl
• Languages of publication: EN

Abstracts

EN

Our previous studies suggested that acylation of the N-terminus of several known B2 antagonists with various kinds of bulky acyl groups consistently improved their antagonistic potency in rat blood pressure assay. On the other hand, our earlier observations also seemed to suggest that the effects of acylation on the contractility of isolated rat uterus depended substantially on the chemical character of the acyl group, as we observed that this modification might either change the range of antagonism or even transform it into agonism. Bearing all this in mind, we decided to synthesize seven new analogues of bradykinin by N-terminal acylation with various acyl groups of a moderately potent B2 antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe-Thi-Arg. The analogues were tested in vitro for their blood pressure-lowering and uterotonic activities. The modifications either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, all seven substituents negatively influenced the interaction with the rat uterine receptors. Our results may be helpful for designing new B2 agonists and antagonists.

Keywords

EN

rat blood pressure assay; bradykinin; rat uterotonic test in vitro; B2 antagonists

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 1
• Pages: 193-198

Dates

published

2007

received

2006-10-31

revised

2006-12-07

accepted

2006-12-18

(unknown)

2007-01-09

Contributors

author

Olga Labudda

• Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

author

Tomasz Wierzba

• Department of Physiology, Medical University of Gdańsk, Gdańsk, Poland

author

Dariusz Sobolewski

• Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

author

Małgorzata Śleszyńska

• Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

author

Łukasz Gawiński

• Department of Physiology, Medical University of Gdańsk, Gdańsk, Poland

author

Marketa Plackova

• Group of Peptide Biochemistry, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

author

Jiřina Slaninová

• Group of Peptide Biochemistry, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

author

Adam Prahl

• Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland

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