Development of photolabile caged analogs of endothelin-1.

S. Bourgault (1) , M. Létourneau (1) , A. Fournier (1)

1 INRS-IAF - Institut Armand Frappier

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.

Domaines: Toxicologie

S. Bourgault, M. Létourneau, A. Fournier. Development of photolabile caged analogs of endothelin-1.. Peptides, 2007, 28 (5), pp.1074-82. ⟨10.1016/j.peptides.2007.02.013⟩. ⟨pasteur-00819999⟩