Aspartic acid scaffold in bradykinin B1 antagonists

József Huszár, Zoltán Timár, Ferenc Bogár, Botond Penke, Róbert Kiss, Krisztina Katalin Szalai, Éva Schmidt, Andrea Papp, György Keserü

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2 Citations (Scopus)


Several novel bradykinin B1 receptor (B1R) antagonists were synthesized utilizing a new aspartic acid scaffold. This core is derived from the highly potent dihydroquinoxalinone scaffold published recently by researchers at Merck (Ha et al. Biochem. Biophys. Res. Commun. 2005, 331, 159-166).Despite the considerably limited chemical space of B1 antagonists, the synthesized compounds still showed significant biological activity. None of the four most potent compounds showed significant activity on the bradykinin B2 receptor (B2R), consequently they can be considered as valuable starting points for designing more potent and selective B1 antagonists. Furthermore, the synthesis of these aspartic acid derivatives is much simpler than that of the original Merck compounds suggesting efficient parallel synthesis approaches during their optimization. Docking known and novel B1 antagonists into the refined B1R homology model including the second extracellular loop (EC2) underlined the importance of this loop in ligand binding. Comparative bindingmode analysis revealed that our novel compounds bind similar to the dihydroquinoxalinone template. Our results indicate that the rigid core of the dihydroquinoxalinone containing B1 antagonists is not crucial for maintaining B1 activity.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalJournal of Peptide Science
Issue number6
Publication statusPublished - Jul 13 2009



  • B1 antagonists
  • Binding modes
  • Bradykinin
  • Docking
  • Peptidomimetic

ASJC Scopus subject areas

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

Cite this

Huszár, J., Timár, Z., Bogár, F., Penke, B., Kiss, R., Szalai, K. K., Schmidt, É., Papp, A., & Keserü, G. (2009). Aspartic acid scaffold in bradykinin B1 antagonists. Journal of Peptide Science, 15(6), 423-434.