Development and pharmacological characterization of "caged" urotensin II analogs.

Steve Bourgault (1) , Myriam Létourneau (2) , Alain Fournier (2)

1 Laboratoire d'études moléculaires et pharmacologiques des peptides
2 INRS-IAF - Institut Armand Frappier

Urotensin-II (U-II) is a cyclic 11-amino acid peptide known as a potent mammalian vasoconstrictor. To study some purported intracellular actions of U-II, masked analogs of this peptide, becoming biologically active only upon UV exposure, were developed. Those analogs described as "caged" were derivatized with a photolabile 4,5-dimethoxynitrobenzyl group on the side chain of Lys-8 or Tyr-9. Both caged analogs of U-II showed a major decrease in their affinity towards the UT receptor. Nevertheless, upon UV irradiation, the native and biologically active U-II peptide was recovered. Thus, this work describes the development of new "caged" U-II derivatives and demonstrates that vasoactivity of U-II can be controlled by masking and unmasking two key residues.

Mots clés: Urotensin-II; Caged; Photolabile; Dimethoxynitrobenzyl

Domaines: Toxicologie

Steve Bourgault, Myriam Létourneau, Alain Fournier. Development and pharmacological characterization of "caged" urotensin II analogs.. Peptides, 2005, 26 (8), pp.1475-80. ⟨10.1016/j.peptides.2005.03.019⟩. ⟨pasteur-00820036⟩