INFLUENCE OF C-TERMINAL MODIFICATIONS OF BRADYKININ ANTAGONISTS ON THEIR ACTIVITY

In the present study we have described the synthesis and some pharmaco logical properties of four new analogues of bradykinin (BK). Two pepti des were designed by substitution of positions 7 and 8 of known B-2 an tagonists with N-methyl-L-phenylalanine [Phe(Me)]. The next two analog ues were obtained by replacement of D-Phe residue in position 7 of kno wn B-2 antagonist with 1-naphthyl-D-alanine or 2-naphthyl-D-alanine. T he antagonistic potency of peptides was assessed by their ability to i nhibit vasodepressor response to exogenous bradykinin in conscious rat s. Although our studies demonstrated disadvantegous influence of Phe(M e)(7, 8) modification for B-2 antagonism, we showed that D-amino acid residue in position 7 of BK antagonists may be replaced by suitable L- amino acid residue. As regards (D-Nal)(7) substitution, we found strik ingly different antagonistic potencies of analogues which differ only in the presence of D-1-Nal and D-2-Nal. We assume that it is due to di fferent conformations of these peptides, proving the importance of the shape of the C-terminal part of B-2 antagonists for their activity.