Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents

0377892 - ÚOCHB 2013 RIV US eng J - Journal Article
Sleszynska, M. - Wierzba, T. H. - Malinowski, K. - Tůmová, Tereza - Lammek, B. - Slaninová, Jiřina - Prahl, A.
Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents.
International Journal of Peptide Research and Therapeutics. Roč. 18, č. 2 (2012), s. 117-124. ISSN 1573-3149. E-ISSN 1573-3904
Institutional research plan: CEZ:AV0Z40550506
Keywords : bradykinin analogues * B-2 receptor antagonists * bulky acyl groups * in vivo rat blood pressure test * in vitro rat uterus test
Subject RIV: CE - Biochemistry
Impact factor: 1.280, year: 2012

In the current work we present some pharmacological characteristics of ten new analogues of bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) modified in the N-terminal part of the molecule with a variety of acyl substituents. Of the many acylating agents used previously with B-2 receptor antagonists, the following residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12-aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2-naphthoic acid. Biological activity of the compounds was assessed in the in vivo rat blood pressure test and the in vitro rat uterus test. Surprisingly, N-terminal substitution of the bradykinin peptide chain itself with aforementioned groups resulted in antagonists of bradykinin in the pressor test and suppressed agonistic potency in the uterotonic test. These interesting findings need further studies as they can be helpful for designing more potent B-2 receptor blockers.
Permanent Link: http://hdl.handle.net/11104/0209919