Urantide conformation and interaction with the urotensin-II receptor.

Abstract

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 previously identified the compound termed urantide (H-Asp-c[Pen-Phe-DTrp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT receptor (UTR) antagonist described to date. Urantide may have potential clinical value in the treatment of atherosclerosis. In the present study, we studied the conformational preferences of urantide in DPC micelles and developed a urantide/UTR interaction model. This model can help the design of novel peptides and small molecules as UTR antagonists.

• Authors: Diego Brancaccio, Antonio Limatola, Pietro Campiglia, Isabel Gomez-Monterrey, Ettore Novellino, Paolo Grieco, Alfonso Carotenuto
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 347 Issue 3 Pg. 185-92 (Mar 2014) ISSN: 1521-4184 [Electronic] Germany
• PMID: 24357333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Peptide Fragments
• Receptors, G-Protein-Coupled
• UTS2R protein, human
• Urotensins
• urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-

Topics

• Binding Sites
• Computer-Aided Design
• Drug Design
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Docking Simulation
• Peptide Fragments (chemistry, metabolism, pharmacology)
• Protein Conformation
• Receptors, G-Protein-Coupled (antagonists & inhibitors, chemistry, metabolism)
• Urotensins (chemistry, metabolism, pharmacology)