title: Development of photolabile caged analogs of endothelin-1.
abstract: Photoactivable caged analogs of endothelin-1 (ET-1) were obtained after derivatization with the photolabile 4,5-dimethoxynitrobenzyl (DMNB) group. This was achieved by the incorporation of N-alpha-Fmoc caged building blocks of Lys, Asp, Glu and Tyr during the solid phase peptide synthesis step. The C-terminal carboxylic function was also derivatized. However, difficulties were encountered with the introduction of the Asp and Glu photoactivable building blocks. As a matter of fact, formation of an aminosuccinyl derivative, through cyclization of the Asp(ODMNB) residue, and the formation of a pyrrolidone ring from the Glu(ODMNB) residue were highly favored by the electronic properties of the photocleavable function. ET-1 analogs were also tested in the ET(A) and ET(B) paradigms and specific pharmacological profiles were obtained for each peptide.
authors.affiliation: Laboratoire d'Etudes Moléculaires et Pharmacologiques des Peptides, INRS - Institut Armand-Frappier, Institut National de la Recherche Scientifique, 245 Boul. Hymus, Pointe-Claire, Que., Canada H9R 1G6. steve.bourgault@iaf.inrs.ca
authors.forename: S
authors.initials: S
authors.lastname: Bourgault
authors.forename: M
authors.initials: M
authors.lastname: Létourneau
authors.forename: A
authors.initials: A
authors.lastname: Fournier
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects / Q000528:radiation effects; D010777:Photochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000819:agonists; D044023:Receptor, Endothelin B / Q000819:agonists; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014466:Ultraviolet Rays; D014661:Vasoconstriction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000596:Amino Acids; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B