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 His4?Pro5 dipeptide sequence by the constrained Trp analogue Aia?Gly, in combination with ?2hVal substitution at the N-terminus, provided a new stable analogue H-(R)-?2hVal-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.

Publication year:2009

Keywords:Angiotensin IV, insulin-regulated aminopeptidase (IRAP), AT4 receptor, beta-homo-amino acids, aminopeptidase N (AP-N), conformational constraints, Organic & medicinal chemistry