ANTAGONISTS OF BRADYKININ MODIFIED WITH CONFORMATIONALLY RESTRICTED DIPEPTIDE FRAGMENT

Four new analogues of bradykinin (BK) were designed, synthesized and b ioassayed. The analogues were designed by introduction of the conforma tionally restricted dipeptide fragment D-Phe-D-Phe into positions 6, 7 or 7, 8 of an previously synthesized antagonist. The antagonistic pot ency of peptides was assessed by their ability to inhibit vasodepresso r response to exogenous bradykinin in conscious rats. We proved the im portance of appropriate localization of the modification used in the m olecule for the value of antagonistic activity. We also demonstrated t hat acylation of the N-terminus of the new analogues with 1-adamantane acetic acid did not increase, as previously considered, antagonistic p otencies of the resulting peptides. Our study, besides providing new i nformation about the structure-activity relationship of bradykinin ant agonists, resulted in compounds, which may be useful for clarifying th e role of BK in various physiological effects.