Potent bradykinin antagonists containing N-benzylglycine or N-benzyl-l-alanine in position 8

• Published in: The journal of peptide research 2004-01, Vol.63 (1), p.29-35
• Main Authors: Dawidowska, O., Wierzba, T.H., Prahl, A., Kowalczyk, W., Derdowska, I., Neubert, K., Zabrocki, J., Olejniczak, B., Juzwa, W., Lammek, B.
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - chemistry; Animals; B2 antagonists; Blood Pressure - drug effects; bradykinin; Bradykinin - analogs & derivatives; Bradykinin - antagonists & inhibitors; conformational constraints; Glycine - analogs & derivatives; Glycine - chemistry; Male; N-Benzyl-l-alanine; N-Benzylglycine; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Oligopeptides - pharmacology; rat blood pressure assay; Rats; Rats, Wistar
• ISSN: 1397-002X; 1399-3011
• DOI: 10.1046/j.1399-3011.2004.00101.x

:  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.