title: Angiotensin II analogues with N-terminal lactam bridge cyclization: an overview on AT1receptor activation and tachyphylaxis.
abstract: 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 AT1activation 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-(Lys1a)]-AngII and Cyclo (0-1a) [Asp0, endo-(Orn1a)]-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.
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil. pelopes2@yahoo.com.br.
authors.forename: Flávio Lopes
authors.initials: FL
authors.lastname: Alves
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
authors.forename: Vani Xavier
authors.initials: VX
authors.lastname: Oliveira
authors.affiliation: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil. amiranda@unifesp.br.
authors.forename: Antonio
authors.initials: A
authors.lastname: Miranda
mesh_terms: D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002942:Circular Dichroism; D006224:Cricetinae; D003412:Cricetulus; D003500:Cyclization; D005748:Gastric Fundus / Q000187:drug effects / Q000502:physiology; D007769:Lactams / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: D007769:Lactams; D008024:Ligands; D010455:Peptides; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II
keywords: angiotensin II; lactam bridge; peptides; synthesis; tachyphylaxis