The replacement of His(4) in angiotensin IV by conformationally constrained residues provides highly potent and selective analogues.
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.
Lukaszuk
Aneta
A
Department of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Demaegdt
Heidi
H
Feytens
Debby
D
Vanderheyden
Patrick
P
Vauquelin
Georges
G
Tourwé
Dirk
D
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
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