Interaction of linear and cyclic peptide antagonists at the human B(2) kinin receptor

Peptides. 2002 Aug;23(8):1457-63. doi: 10.1016/s0196-9781(02)00081-5.


The ligand receptor interactions involving the C-terminal moiety of kinin B(2) receptor antagonists Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-Dtic-Oic-Arg-OH), MEN 11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-Dtic-Oic-Arg)c(7gamma-10alpha)) and a series of analogs modified in position 10 were investigated by radioligand-binding experiments at the wild type (WT) and at the Ser(111)Ala and Ser(111)Lys mutant human kinin B(2) receptors. Icatibant and [Lys(10)]-Icatibant maintained the same high affinity towards the three receptors. For Icatibant-NH(2), [Ala(10)]-Icatibant, MEN 11270 and [Glu(10)]-MEN 11270, the changes in affinity at the WT and Ser(111)Lys receptors indicated that the presence of a net positive or negative charge at the C-terminal moiety of these peptides caused a decrease in affinity to the WT receptor and that Ser(111) residue is in proximity of the side chain of residue 10. The changes in affinity measured with [desArg(10)]-Icatibant and [desArg(10)]-Icatibant-NH(2), moreover, confirmed that a C-terminal charge compensation between the positive charge of Arg(10) side chain and the C-terminal free carboxylic function favours a high affinity interaction.

MeSH terms

  • Animals
  • Bradykinin / analogs & derivatives*
  • Bradykinin / metabolism*
  • Bradykinin Receptor Antagonists*
  • CHO Cells
  • Cricetinae
  • Humans
  • Mutagenesis, Site-Directed
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin / genetics
  • Receptors, Bradykinin / metabolism
  • Structure-Activity Relationship


  • Bradykinin Receptor Antagonists
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • icatibant
  • Bradykinin