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

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

Research output: Article

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 - márc. 2007

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Bradykinin
Scaffolds
Bradykinin B2 Receptors
Conformations
CHO Cells
Dipeptides
Ileum
Smooth Muscle
Guinea Pigs
Ligands
Muscle
Assays
Peptides
icatibant

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Ballet, S., De Wachter, R., Van Rompaey, K., Tömböly, C., Feytens, D., Töth, G., ... 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

Bradykinin analogs containing the 4-amino-2-benzazepin-3-one scaffold at the C-terminus. / Ballet, S.; De Wachter, R.; Van Rompaey, K.; Tömböly, C.; Feytens, D.; Töth, G.; Quartara, L.; Cucchi, P.; Meini, S.; Tourwé, D.

In: Journal of Peptide Science, Vol. 13, No. 3, 03.2007, p. 164-170.

Research output: Article

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, vol. 13, no. 3, pp. 164-170. https://doi.org/10.1002/psc.827
Ballet, S. ; De Wachter, R. ; Van Rompaey, K. ; Tömböly, C. ; Feytens, D. ; Töth, G. ; Quartara, L. ; Cucchi, P. ; Meini, S. ; Tourwé, D. / Bradykinin analogs containing the 4-amino-2-benzazepin-3-one scaffold at the C-terminus. In: Journal of Peptide Science. 2007 ; Vol. 13, No. 3. pp. 164-170.
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AU - Ballet, S.

AU - De Wachter, R.

AU - Van Rompaey, K.

AU - Tömböly, C.

AU - Feytens, D.

AU - Töth, G.

AU - Quartara, L.

AU - Cucchi, P.

AU - Meini, S.

AU - Tourwé, D.

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N2 - 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.

AB - 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.

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KW - 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones

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KW - Bradykinin

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