UT receptor peptide antagonist-UFP 803

Introduction 

UFP-803 (H-Asp-c[Pen-Phe-DTrp-Dab-Tyr-Cys]-Val-OH), [Pen ⁵, DTrp ⁷, Dab ⁸] U-II (4-11), is a peptidic UT (urotensin-II receptor) receptor ligand. It is generated from a potent UT receptor antagonist, urantide ([Pen ⁵, DTrp ⁷, Orn ⁸] U-II (4-11), which has the agonist activity at human recombinant UT receptors in a Ca ²⁺ mobilization assay. The experiments by Guerrini et al. showed that the substitution of Orn ⁸ with diaminobutyric acid in [Dab ⁸] U-II leads to a reduction in potency, but also attenuates the efficacy of the peptide, so this chemical modification has been applied to the urantide sequence to generate the peptide UFP-803.

Biological Activity

As a derivative of Urotensin-II (U-II), UFP-803 has a biological effect of antagonizing U-II in a dose-dependent manner. In animal experiments, 10nmol/kg of UFP-803 completely inhibited U-II-induced vasoconstriction, but its efficacy was lower than that of urantide, and it was found to have a weak effect of promoting intracellular Ca ²⁺ transfer in hamster ovary cells. Using RNA interference-silenced UT mRNA expression, UFP-803 and urantide have a good correlation with UT antagonism. In the study of the nervous system, UFP-803 can reverse U-II to promote the release of norepinephrine from cerebral cortical cells and inhibits U II to maintain arousal.

Function

The UT receptor system is implicated in the pathogenesis of a number of cardiovascular, renal and metabolic disorders, and Urotensin-II's action can be mediated by UT receptors. UT receptor is expressed in a variety of peripheral organs, such as kidney, liver, endocrine glands, and especially cardiocascular tissues. In vitro and in vivo assays, UFP-803 is a potent and selective UT receptor ligand. Although this peptide exhibits a certain receptor agonist activity, it exhibits its antagonistic activity to the greatest extent in these experiments. Moreover, UFP 803 can be a chemical template for identifying novel UT receptor ligands, as well as a pharmacological tool for in vitro and studying the role played by the U-II/UT receptor system in physiology and pathology in vivo.

References

1. Camarda, V., Spagnol, M., Song, W., Vergura, R., Roth, A. L., Thompson, J. P., ... & Cavanni, P. (2006). In vitro and in vivo pharmacological characterization of the novel UT receptor ligand [Pen5, DTrp7, Dab8] urotensin II (4–11) (UFP‐803). British journal of pharmacology, 147 (1), 92-100.

2. Leprince, J., Chatenet, D., Dubessy, C., Fournier, A., Pfeiffer, B., Scalbert, E., ... & Guilhaudis, L. (2008). Structure–activity relationships of urotensin II and URP. Peptides, 29 (5), 658-673.

3. Merlino, F., Di Maro, S., Munaim Yousif, A., Caraglia, M., & Grieco, P. (2013). Urotensin-II ligands: an overview from peptide to nonpeptide structures. Journal of amino acids, 2013.