Potent bradykinin antagonists containing N-benzylglycine or N-benzyl-l-alanine in position 8.
Two new analogues of a previously designed bradykinin (BK) antagonist, d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Phe-Thi-Arg, substituted in position 8 by N-benzylglycine and N-benzyl-l-alanine were designed, synthesized and bioassayed. The results show an impressive enhancement of B2 antagonistic potencies of both peptides in comparison with the model. In two further analogues these modifications were combined with acylation of the N-terminus with 1-adamantanacarboxylic acid. Acylated analogues exhibited higher antagonistic potency in comparison with the parent compounds, however, the range of effect was not as high as in previously described cases. The activity of analogues was assessed by their ability to inhibit vasodepressor response to exogenous BK (rat blood pressure test). Our results may be of value in the design of more potent BK antagonists.
Dawidowska
O
O
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. olad@chemik.chem.univ.gda.pl
Prahl
A
A
Kowalczyk
W
W
Derdowska
I
I
Lammek
B
B
Wierzba
T H
TH
Juzwa
W
W
Neubert
K
K
Zabrocki
J
J
Olejniczak
B
B
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C490719:N-benzylalanine; D009842:Oligopeptides; C423606:N-benzylglycine; D000409:Alanine; D001920:Bradykinin; D005998:Glycine