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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Urotensin-II receptor peptide agonists.

Urotensin II (U-II) has been known for over 30 years as an important teleost fish hormone, but only recently has it been recognized as the endogenous ligand of a new human G-protein-coupled receptor ( GPCR) homologous to the GPR14 orphan receptor from rat. Human U-II was found to be a potent vasoconstrictor, widely distributed in human tissues, possibly contributing to several human cardiovascular diseases. It thus has become a major target of medicinal chemistry research. The common structural feature of U-II peptides from different species is the C-terminal portion, characterized by the disulfide bridged cyclic hexapeptide Cys-Phe-Trp-Lys-Tyr-Cys. The few structure-activity relationship studies reported to date attributed a critical role to this portion, with the Trp-Lys-Tyr motif appearing as the key determinant of U-II bioactivity. Consequently, this shorter cyclic peptide was used as a template for the development of several synthetic analogues, among which a superagonist, termed P5U: H-Asp-cyclo(Pen-Phe-Trp-Lys-Tyr-Cys)-Val-OH. Conformational studies confirmed the important role of hU-II C-terminal cyclic portion, enabling the development of 3D pharmacophore models. These findings should lead to the design of new, potent and selective analogues, acting as agonist or antagonist at the human U-II receptor, finally contributing to a deeper comprehension of the (patho)physiological significance of this peptide.[1]


  1. Urotensin-II receptor peptide agonists. Carotenuto, A., Grieco, P., Novellino, E., Rovero, P. Medicinal research reviews. (2004) [Pubmed]
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