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New insight into the binding mode of peptides at urotensin‐II receptor by Trp‐constrained analogues of P5U and urantide
Author(s) -
Carotenuto Alfonso,
Auriemma Luigia,
Merlino Francesco,
Limatola Antonio,
Campiglia Pietro,
GomezMonterrey Isabel,
Villa Bianca Roberta d'Emmanuele,
Brancaccio Diego,
Santicioli Paolo,
Meini Stefania,
Maggi Carlo Alberto,
Novellino Ettore,
Grieco Paolo
Publication year - 2013
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.2498
Subject(s) - chemistry , peptide , residue (chemistry) , receptor , stereochemistry , urotensin ii , disulfide bond , ligand (biochemistry) , antagonist , biochemistry
Urotensin II (U‐II) is a disulfide bridged peptide hormone identified as the ligand of a G‐protein‐coupled receptor. Human U‐II (H‐Glu‐Thr‐Pro‐Asp‐c[Cys‐Phe‐Trp‐Lys‐Tyr‐Cys]‐Val‐OH) has been described as the most potent vasoconstrictor compound identified to date. We have recently identified both a superagonist of human U‐II termed P5U (H‐Asp‐c[Pen‐Phe‐Trp‐Lys‐Tyr‐Cys]‐Val‐OH) and the compound termed urantide (H‐Asp‐c[Pen‐Phe‐ d ‐Trp‐Orn‐Tyr‐Cys]‐Val‐OH), which is the most potent UT receptor peptide antagonist described to date. In the present study, we have synthesized four analogues of P5U and urantide in which the Trp 7 residue was replaced by the highly constrained l ‐Tpi and d ‐Tpi residues. The replacement of the Trp 7 by Tpi led to active analogues. Solution NMR analysis allowed improving the knowledge on conformation–activity relationships previously reported on UT receptor ligands. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.