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Small potent ligands to the insulin‐regulated aminopeptidase (IRAP)/AT 4 receptor
Author(s) -
Axén Andreas,
Andersson Hanna,
Lindeberg Gunnar,
Rönnholm Harriet,
Kortesmaa Jarkko,
Demaegdt Heidi,
Vauquelin Georges,
Karlén Anders,
Hallberg Mathias
Publication year - 2007
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.859
Subject(s) - chemistry , aminopeptidase , ligand (biochemistry) , angiotensin ii , peptide , receptor , angiotensin iii , biochemistry , angiotensin receptor , stereochemistry , oligopeptide , amino acid , leucine
Angiotensin IV analogs encompassing aromatic scaffolds replacing parts of the backbone of angiotensin IV have been synthesized and evaluated in biological assays. Several of the ligands displayed high affinities to the insulin‐regulated aminopeptidase (IRAP)/AT 4 receptor. Displacement of the C ‐terminal of angiotensin IV with an o ‐substituted aryl acetic acid derivative delivered the ligand 4 , which exhibited the highest binding affinity ( K i = 1.9 n M ). The high affinity of this ligand provides support to the hypothesis that angiotensin IV adopts a γ‐turn in the C ‐terminal of its bioactive conformation. Ligand ( 4) inhibits both human IRAP and aminopeptidase N‐activity and induces proliferation of adult neural stem cells at low concentrations. Furthermore, ligand 4 is degraded considerably more slowly in membrane preparations than angiotensin IV. Hence, it might constitute a suitable research tool for biological studies of the (IRAP)/AT 4 receptor. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.