Dehydrophenylalanyl analogs of bradykinin: Synthesis and biological activities

We have synthesized three analogs of the potent vasodilator peptide bradykinin, ArgProProGlyPhe SerProPheArg (BK), containing dehydrophenylalanine (Δ^zPhe) in place of the phenylalanyl residues at positions 5 and/or 8. The analogs, [Δ^zPhe⁵]BK, [Δ^zPhe⁸]BK, and [Δ^zPhe^5,8]BK, were assayed for their effects on isolated smooth muscle tissues and on the systemic arterial blood pressure of rats. In these assays [Δ^zPhe⁵]BK showed considerably high biological activities, particularly in terms of its blood pressure-lowering effects, being over 23 times more potent than BK when given intravenously. [Δ^zPhe⁸]BK was less potent than BK and [Δ^zPhe^5,8]BK had effects comparable to those of BK. All three synthetic analogs appear to be more resistant than BK to enzymic degradation during passage through the pulmonary vascular bed.