Bradykinin analogs containing beta-homoamino acids

Abstract

Two new analogs of bradykinin, [8-beta-homophenylalanine]- and [7-beta-homoproline]bradykinin, have been synthesized by the solid-phase technique. In the anesthetized rat, [7-beta-HPro]bradykinin was equipotent with bradykinin and 30-100 times more potent than [8-beta-HPhe]bradykinin in vasodepressor activity. Both analogs were resistant to degradation in vitro by dipeptidylcarboxypeptidase from rabbit lung. Only the 7-beta-HPro analog seemed to be resistant to this type of degradation in vivo, since its hypotensive effect in the anesthetized rat was not potentiated by SQ 20881 (BPP9a), an inhibitor of dipeptidylcarboxypeptidase.