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New acylated bradykinin analogues: effect on rat blood pressure and rat uterus
Author(s) -
Dawidowska Olga,
Prahl Adam,
Wierzba Tomasz,
Nowakowski Łukasz,
Kowalczyk Wioleta,
Slaninová Jiřina,
Lammek Bernard
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.646
Subject(s) - bradykinin , uterotonic , acylation , chemistry , antagonist , stereochemistry , receptor , potency , antagonism , pharmacology , peptide , uterus , medicine , endocrinology , biochemistry , in vitro , oxytocin , biology , catalysis
Abstract It was previously reported that acylation of the N ‐terminus of several known B 2 antagonists with various types of bulky acyl groups consistently improved their antagonistic potency in the rat blood pressure assay. On the other hand, earlier results seem to suggest that the effects of acylation on the contractility of isolated rat uterus depend substantially on the chemical character of the acyl group, as it was observed that this modification may either change the range of antagonism or even transform it into agonism. Bearing all this in mind, three new analogues of bradykinin were designed by modifying the moderately potent B 2 antagonist, previously synthesized by Stewart's group, D ‐Arg‐Arg‐Pro‐Hyp‐Gly‐Thr‐Ser‐ D ‐Phe‐Thi‐Arg. New analogues were obtained by acylation of the N ‐terminus of the above peptide with succinic acid, 12‐aminododecanoic acid and 4‐aminobenzoic acid in order to confirm whether either the positive or the negative charge on the N ‐terminal end of the peptide is responsible for the transformation of activity. The activity of analogues was assessed on blood pressure and in uterotonic in vitro tests. The modifications proposed either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, the three substituents, depending on their chemical character, differently influenced the interaction with the rat uterine receptors. The results may be of value in the design of new B 2 agonists and antagonists. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.