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Conformationally restricted cyclic analogues of angiotensin II (ANG II), Asp-Arg-Val-Tyr-Val-His-Pro-Phe, with a link between positions 3 and 5 have considerable biological activity. It is proposed that the spatial arrangement of the pharmacophore groups of Tyr, His and Phe side chains and the C-terminal carboxyl group in ANG II and active analogues is similar. Conformational analysis of ANG II and two cyclic analogues c[Sar, Lys,Glu]ANG II and c[Sar,Hcy,Mpt]ANG II was performed, and a geometrical comparison of the low-energy conformations of these compounds allowed one to propose a model of receptor-bound conformation in terms of the spatial arrangement of the pharmacophore groups. This model is characterised by the close spatial location of the His-Phe side chains and the Tyr C-terminal carboxyl group and is stabilised by the electrostatic interaction of Arg and the C-terminal carboxyl group. [ABSTRACT FROM AUTHOR]