Samanen, J., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States, Peptide Chemistry Department, Smith Kline and French Laboratories, P.O. 1539, King of Prussia, PA 19406-0939, United States
Narindray, D., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Cash, T., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Brandeis, E., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Adams Jr., W., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Yellin, T., Peptide Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Eggleston, D., Structural/Physical Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
DeBrosse, C., Analytical Chemistry Department, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939, United States
Regoli, D., Department of Pharmacology, University of Sherbrooke, Sherbrooke, Que. J1H 5N4, Canada

Amino acids with lipophilic side chains that contain more than one functional group on the β-carbon, i.e. a β-branched hydrocarbon moiety, are required in position 5 of angiotensin II (AII) analogue with potent agonist activity. This requirement for agonist activity does not follow for AII analogues with potent antagonist activity. Straight-chain amino acids may be substituted into position 5 of [Sar1,X5,Ile8]AII with retention or enhancement of antagonist activity, e.g. (X5, pA2 rabbit aorta) Phe, 9.15; Tyr, 9.6; His, 9.0; Arg, 9.0; Glu, 9.0; Nle, 8.85, compared to Ile, 9.1. β-Branched side chains can still enhance the antagonist activities of [Sar1,X5,Ile8]AII analogues, e.g. X5 = (βMe)Phe, pA2 = 9.3. An X-ray crystal structure of the Boc-(βMe)Phe DCHA salt, prepared for the synthesis of [Sar1,(βMe)Phe6,Ile8]AII, revealed an S,S configuration of α- and β-carbon atoms. Contrary to previous literature reports, chemical nonequivalence of the δ-protons of Pro was observed in the 1H NMR spectra of [Sar1,X5,Ile8]AII analogues bearing both β-branched X5 side chains (X5 = Ile) and non-β-branched X5 side chains (X5 = Ala, His). © 1989 American Chemical Society.