Conformationally restricted analogs of angiotensin II: titration and biological activity.
1. Six conformationally restricted analogues of angiotensin II containing one disulfide bridge were synthesized by the solid-phase method. 2. These cyclic analogues were titrated electrometrically and spectrophotometrically and their biological activities were assayed on the isolated guinea pig ileum and rat blood pressure. 3. The conformation restrictions led to significant differences in the pKa values of the titratable groups in all six analogs. 4. The comparison of titration data between the cyclic and linear analogs of angiotensin II indicates that in the pH range 4 to 9, angiotensin II has a preferential folded conformation. An expanded conformation is assumed to occur at pH below 4 and above 9. 5. The biological activities of all cyclic analogs were less than 0.2% of the activity of angiotensin II in both bioassays.
Miranda
A
A
Departamento de Biofísica, Escola Paulista de Medicina, São Paulo, Brasil.
Juliano
L
L
D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008968:Molecular Conformation; D051381:Rats
D000804:Angiotensin II; D000803:Angiotensin I