DESIGN AND SYNTHESIS OF NEW BRADYKININ ANTAGONISTS WITH N-TERMINAL ACYLATION

Synthesis and some pharmacological properties of eight new analogues o f bradykinin are described. Five peptides were designed to gain more i nformation about features of N-terminal bulky acyl groups suitable for improvement of B-2-antagonistic properties. Two other compounds were synthesized in order to learn how removal of N-terminal D-Arg residue or replacement of D-Arg-Arg with a Lys-Lys fragment would influence B- 2-antagonism. The last peptide was obtained in order to check whether inversion of configuration of C-terminal Arg residue in the molecule o f potent B-2-blocker will decrease its antagonistic activity. The B-2- antagonistic potency of analogues was evaluated by their ability to in hibit vasodepressor response to exogenous bradykinin in conscious rats . Thus it appears that not only the size of an acyl group attached to the N-terminus of peptide, but also chemical features of the substitue nt are important for B-2-antagonism.