Conformational constraints in angiotensin IV to probe the role of Tyr², Pro⁵ and Phe⁶

Aneta Lukaszuk, Heidi Demaegdt, Isabelle Van den Eynde, Patrick Vanderheyden, Georges Vauquelin, Dirk Tourwé

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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 Tyr¹, while only e-β-MePhe⁶ substitution resulted in an AngIV analog with high IRAP potency and selectivity versus AP-N or the AT₁ receptor. This indicates an important role of the orientation of the Phe⁶ for inducing selectivity. Pro⁵ replacement with 2-aminocyclopentanecarboxylic acid maintained IRAP potency and abolished AT₁ affinity. These results confirm the importance of conformational constrained amino acids to generate selectivity in bioactive peptides.

Original languageEnglish
Pages (from-to)545-553
Number of pages9
JournalJournal of Peptide Science
Issue number8
Publication statusPublished - Aug 2011


  • Aminopeptidases
  • Angiotensin II
  • Animals
  • Biocatalysis
  • CHO Cells
  • Cell Membrane
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Phenylalanine
  • Proline
  • Protein Conformation
  • Spectrophotometry, Atomic
  • Substrate Specificity
  • Tyrosine
  • Research Support, Non-U.S. Gov't


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