Angiotensin II analogues with N-terminal lactam bridge cyclization: an overview on AT 1 receptor activation and tachyphylaxis.

Angiotensin II (AngII) is the final active product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. To investigate the effect of N-terminal cyclization on AT ₁ activation and tachyphylaxis, we designed conformationally constrained analogues with an i-(i + 1) lactam bridge. All analogues presented the same binding coefficient and tachyphylactic index, but some of them such as Cyclo (0-1a) [Glu ⁰ , endo-(Lys ^1a )]-AngII and Cyclo (0-1a) [Asp ⁰ , endo-(Orn ^1a )]-AngII showed higher potency. The same tachyphylactic index presented by AngII and cyclic analogues was surprising. We expected a variation after the modification of AngII N-terminal region.
(© 2016 John Wiley & Sons A/S.)