title: Novel analogues of bradykinin conformationally restricted in the C-terminal part of the molecule.
abstract: In the present work, achiral non-coded amino acids, N-(Bzl)-Gly, X(1) or X(2) , were substituted at position 7 of the model B(2) receptor antagonist [D-Arg(0) , Hyp(3) , Thi(5, 8) , D-Phe(7) ]-BK. The N-terminal amino group of the analogues was either free or acylated with 1-Aca or Aaa. Biological activity of the compounds was assessed in the in vitro rat uterus test and the in vivo rat blood pressure test. The X(1) (7) substitution resulted in a decrease in antagonistic potency of the new peptide in both assays. The X(2) (7) and N-(Bzl)-Gly(7) substituted analogues showed weak agonistic properties in the rat uterus test. Interestingly, the latter compound exhibited dual activity in the pressor test, i.e. intrinsic vasodepressor action and at the same time a weak antagonistic effect. Acylation of the N-terminus enhanced antagonistic properties of the resulting peptides in the rat blood pressure test in the case of compounds containing X(1) or X(2) modification. Our studies provide new information about structure-activity relationship of the BK antagonists which may be helpful for designing more potent B(2) receptor blockers.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18/19, 80-952 Gdańsk, Poland. slesza@chem.univ.gda.pl
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sleszyńska
authors.forename: Tomasz H
authors.initials: TH
authors.lastname: Wierzba
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Malinowski
authors.forename: Lenka
authors.initials: L
authors.lastname: Borovičková
authors.forename: Izabela
authors.initials: I
authors.lastname: Małuch
authors.forename: Dariusz
authors.initials: D
authors.lastname: Sobolewski
authors.forename: Bernard
authors.initials: B
authors.lastname: Lammek
authors.forename: Jiřina
authors.initials: J
authors.lastname: Slaninová
authors.forename: Adam
authors.initials: A
authors.lastname: Prahl
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
chemical_list: D065094:Bradykinin B2 Receptor Antagonists; D001920:Bradykinin