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Conformational constraints in angiotensin IV to probe the role of Tyr 2 , Pro 5 and Phe 6
Author(s) -
Lukaszuk Aneta,
Demaegdt Heidi,
Van den Eynde Isabelle,
Vanderheyden Patrick,
Vauquelin Georges,
Tourwé Dirk
Publication year - 2011
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1365
Subject(s) - selectivity , chemistry , potency , stereochemistry , amino acid , peptide , biochemistry , in vitro , catalysis
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.