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

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2016
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Alves, Flavio Lopes [UNIFESP]
Oliveira, Vani Xavier, Jr.
Miranda, Antonio [UNIFESP]
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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.
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Chemical Biology & Drug Design. Hoboken, v. 88, n. 5, p. 677-682, 2016.
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