Conformationally restricted analogs of angiotensin II: titration and biological activity

ABSTRACT

1. Six conformationally restricted analogues of angiotension II containing one disulfide bridge were synthesized by the solid-phase method. 2. These cyclic analogues were tirated electrometically and spectrophotometrically and their biological activites were assayed on the isolated guinea pig ileum and rat blood pressure. 3. The conformation restrictions led to significant differnces in the pKa values of a the titratable groups in al six analogs. 4. The comparison of tiration data between the cyclic and linear analogs of angiotension II indicates that in the pH range 4 to 9, angiotension II has a preferential folded conformation. An expanded conformation is assumed to occur at pH below 4 and above 9. 5. The biological activites of all cyclic analogs were less than 0.2% of the activity of angiotension II in toth bioassays