Collect. Czech. Chem. Commun. 1991, 56, 1539-1544

Synthesis and some pharmacological properties of three new bradykinin antagonists

Bernard Lammek, Yi-Xin Wang and Haralambos Gavras

Department of Medicine, Boston University Medical Center, 80 East Concord Street, Boston, MA 02118, U.S.A.


Three new analogues of bradykinin (BK) were designed, synthesized and bio assayed in conscious, unrestrained rats. The analogues were designed by modifying the [D-Arg0, Hyp3, hi5,8, D-Phe7]-BK which was previously synthesized by the Steward group and was considered to be one of the most potent antagonists of BK known to date. It has been reported herein that the introduction of additional D-Arg residue or acylation with propionic acid of the N-terminus of [D-Arg0, Hyp3, Thi5,8, D-Phe7]BK (model peptide) results in analogues with similar or weaker antagonistic potency as compared to the model, respectively. However, the acylation with 1-adamantaneacetic acid results in an analogue with more than ten times enhanced potency and efficacy. All peptides were synthesized by the solid phase method.