title: The replacement of His(4) in angiotensin IV by conformationally constrained residues provides highly potent and selective analogues.
abstract: The histidine residue in angiotensin IV was replaced by various conformationally constrained amino acids. The substitution of the His(4)-Pro(5) dipeptide sequence by the constrained Trp analogue Aia-Gly, in combination with beta(2)hVal substitution at the N-terminus, provided a new stable analogue H-(R)-beta(2)hVal-Tyr-Ile-Aia-Gly-Phe-OH (AL-40) that is a potent ligand for the Ang IV receptor IRAP and selective versus AP-N and the AT1 receptor.
authors.affiliation: Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Aneta
authors.initials: A
authors.lastname: Lukaszuk
authors.forename: Heidi
authors.initials: H
authors.lastname: Demaegdt
authors.forename: Debby
authors.initials: D
authors.lastname: Feytens
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanderheyden
authors.forename: Georges
authors.initials: G
authors.lastname: Vauquelin
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000737:chemistry; D032701:Biomimetics; D016466:CHO Cells; D002264:Carboxylic Acids / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D006639:Histidine; D006801:Humans; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D001381:Azepines; D002264:Carboxylic Acids; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D010649:Phenylalanine; D006639:Histidine; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase