TY - JOUR T1 - Analogues of Angiotensin II with Restricted Conformational Freedom, Including a New Antagonist JF - Molecular Pharmacology JO - Mol Pharmacol SP - 217 LP - 224 VL - 12 IS - 2 AU - JOHN TURK AU - PHILIP NEEDLEMAN AU - GARLAND R. MARSHALL Y1 - 1976/03/01 UR - http://molpharm.aspetjournals.org/content/12/2/217.abstract N2 - Two analogues of angiotensin II (AII) and one analogue of the AII antagonist [1-sarcosine, 8-valine]-angiotensin II ([Sar1, Va18]-AII) have been synthesized which contain a methyl group in the place of a proton on α-carbon 4 or 8. Theoretical studies indicate that these analogues should have restricted conformational freedom. The relatively high activity of the position 4 analogue in the rat uterus and blood pressure assays, when interpreted in the light of previous structure-activity studies, allows the tentative assignment of the torsional angles φ and ψ at position 4 in the receptor-bound conformation of AII. These values differ from those determined for AII in solution. The position 8 analogue, [Sar1, Val(αMe)8]-AII is itself an antagonist and is 7 times more potent in vivo than [Sar1, Val8]-AII. ER -