Conformational analysis of cyclic angiotensin II analogues

✍ Scribed by Juris Balodis; Alexander Golbraikh

• Book ID: 104632886
• Publisher: Springer Netherlands
• Year: 1996
• Tongue: English
• Weight: 298 KB
• Volume: 3
• Category: Article
• ISSN: 1573-3149
• DOI: 10.1007/bf00128107

✦ Synopsis

Conformationally restricted cyclic analogues of angiotensin II (ANG II), Aspl-Arg2-ValLTyr4-ValS-His6-Pro 7-Phe 8, 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 a, His 6 and Phe 8 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 ~, Lys3,GIuS]ANG II and c[Sarl,Hcy3,Mp:]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 His6-Phe 8 side chains and the Tyr 4 C-terminal carboxyl group and is stabilised by the electrostatic interaction of Arg z and the C-terminal carboxyl group.