Development and pharmacological characterization of "caged" urotensin II analogs.
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.
Bourgault
Steve
S
Université du Québec, Laboratoire d'études moléculaires et pharmacologiques des peptides, INRS--Institut Armand-Frappier, Institut National de la Recherche Scientifique, 245 boul. Hymus, Pointe-Claire (Montréal), Que. Canada H9R 1G6.
Létourneau
Myriam
M
Fournier
Alain
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D008297:Male; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects; D010782:Photolysis / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014466:Ultraviolet Rays; D014579:Urotensins / Q000138:chemical synthesis / Q000494:pharmacology / Q000528:radiation effects
D010456:Peptides, Cyclic; D014579:Urotensins; C029677:urotensin II