Bradykinin analogs containing the 4-amino-2-benzazepin-3-one scaffold at the C-terminus

S. Ballet, R. De Wachter, K. Van Rompaey, Cs Tömböly, D. Feytens, G. Töth, L. Quartara, P. Cucchi, S. Meini, D. Tourwé

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7 Citations (Scopus)

Abstract

High affinity peptide ligands for bradykinin (BK) B2 subtype receptor have been shown to adopt a β-turn conformation of the C-terminal tetrapeptlde (H-Arg1-Pro2- Pro3-Gly4-Phe5-Ser6- Pro7-Phe8-Arg9-OH). We investigated the replacement of the Pro7-Phe8 dipeptide moiety in BK or the D-Tic7-Oic8 subunit in HOE140 (H-D-Arg0-Arg1-Pro2- Hyp3-Gly4-Thi5-Ser6- D-Tic7-Oic8-Arg9-OH) by 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one templates (Aba). Binding studies to the human B2 receptor showed a correlation between the affinities of the BK analogs and the propensity of the templates to adopt a β-turn conformation. The L-spiro-Aba-Gly containing HOE140 analog BK10 has the best affinity, which correlates with the known turn-inducing property of this template. All the compounds did not modify basal inositolphosphate (IP) output in B2-expressing CHO cells up to 10 μM concentration. The antagonist properties were confirmed by the guinea pig ileum smooth muscle contractility assay. The new amino-benzazepinone (Aba) substituted BK analogs were found to be surmountable antagonists.

Original languageEnglish
Pages (from-to)164-170
Number of pages7
JournalJournal of Peptide Science
Volume13
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

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Keywords

  • 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones
  • B antagonists
  • Bradykinin
  • HOE 140
  • β-turn conformation

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Ballet, S., De Wachter, R., Van Rompaey, K., Tömböly, C., Feytens, D., Töth, G., Quartara, L., Cucchi, P., Meini, S., & Tourwé, D. (2007). Bradykinin analogs containing the 4-amino-2-benzazepin-3-one scaffold at the C-terminus. Journal of Peptide Science, 13(3), 164-170. https://doi.org/10.1002/psc.827