New insight into the binding mode of peptides at urotensin-II receptor by Trp-constrained analogues of P5U and urantide
Version of Record online: 25 MAR 2013
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 19, Issue 5, pages 293–300, May 2013
How to Cite
Carotenuto, A., Auriemma, L., Merlino, F., Limatola, A., Campiglia, P., Gomez-Monterrey, I., di Villa Bianca, R. d., Brancaccio, D., Santicioli, P., Meini, S., Maggi, C. A., Novellino, E. and Grieco, P. (2013), New insight into the binding mode of peptides at urotensin-II receptor by Trp-constrained analogues of P5U and urantide. J. Peptide Sci., 19: 293–300. doi: 10.1002/psc.2498
- Issue online: 15 APR 2013
- Version of Record online: 25 MAR 2013
- Manuscript Accepted: 27 JAN 2013
- Manuscript Revised: 25 JAN 2013
- Manuscript Received: 19 DEC 2012
- therapeutic peptide;
- constrained tryptophan analogues;
- conformation by NMR
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 Trp7 residue was replaced by the highly constrained l-Tpi and d-Tpi residues. The replacement of the Trp7 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.