RT Journal Article
SR Electronic
T1 Analogues of Angiotensin II with Restricted Conformational Freedom, Including a New Antagonist
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 217
OP 224
VO 12
IS 2
A1 TURK, JOHN
A1 NEEDLEMAN, PHILIP
A1 MARSHALL, GARLAND R.
YR 1976
UL http://molpharm.aspetjournals.org/content/12/2/217.abstract
AB 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.