Angiotensin II analogues with N-terminal lactam bridge cyclization: an overview on AT₁ receptor activation and...

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 AT₁ 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) [Glu⁰ , endo-(Lys^1a )]-AngII and Cyclo (0-1a) [Asp⁰ , 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.