Conformational constraints in angiotensin IV to probe the role of Tyr2, Pro5 and Phe6
✍ Scribed by Aneta Lukaszuk; Heidi Demaegdt; Isabelle Van den Eynde; Patrick Vanderheyden; Georges Vauquelin; Dirk Tourwé
- Book ID
- 105359992
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 279 KB
- Volume
- 17
- Category
- Article
- ISSN
- 1075-2617
- DOI
- 10.1002/psc.1365
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✦ Synopsis
Abstract
The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β‐Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr^1^, while only e‐β‐MePhe^6^ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP‐N or the AT~1~ receptor. This indicates an important role of the orientation of the Phe^6^ for inducing selectivity. Pro^5^ replacement with 2‐aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT~1~ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.