Bradykinin analogs containing the 4-amino-2-benzazepin-3-one scaffold at theC-terminus
| Autor: | Dirk Tourwé, Stefania Meini, Steven Ballet, P. Cucchi, Laura Quartara, Cs. Tömböly, K. Van Rompaey, Debby Feytens, R. De Wachter, Géza Tóth |
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| Rok vydání: | 2007 |
| Předmět: |
Receptor
Bradykinin B2 Protein Conformation Stereochemistry Protein subunit Guinea Pigs Bradykinin Peptide CHO Cells Biochemistry chemistry.chemical_compound Cricetulus Structural Biology Cricetinae Drug Discovery Animals Humans Amino Acid Sequence Receptor Molecular Biology Pharmacology chemistry.chemical_classification Dipeptide Tetrapeptide C-terminus Organic Chemistry Muscle Smooth General Medicine Smooth muscle contraction Benzazepines chemistry Molecular Medicine Muscle Contraction |
| Zdroj: | Journal of Peptide Science. 13:164-170 |
| ISSN: | 1099-1387 1075-2617 |
| DOI: | 10.1002/psc.827 |
| Popis: | High affinity peptide ligands for the bradykinin (BK) B2 subtype receptor have been shown to adopt a β-turn conformation of the C-terminal tetrapeptide (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. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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