NOVEL CAGED COMPOUNDS OF HYDROLYSIS-RESISTANT 8-BR-CAMP AND 8-BR-CGMP- PHOTOLABILE NPE ESTERS

The application of the 1-(2-nitrophenyl) ethyl (NPE) moiety as a photo labile ligand for the release of hydrolysis-resistant 8-Br-cAMP and 8- Br-cGMP was examined. NPE-caged 8-Br-cAMP and 8-Br-cGMP liberate 8-Br- cAMP and 8-Br-cGMP during irradiation with ultraviolet light. The synt hesis procedure resulted in diastereoisomeric mixtures, which were chr omatographically separated into the axial and equatorial isomers of NP E-caged 8-Br-cAMP and 8-Br-cGMP. The hydrolytic stability, solubility and photochemical properties of these derivatives were compared to the previously reported 4,5-dimethoxy-2-nitrobenzyl(DMNB) compounds. We f ound that the axial isomers of NPE-caged 8-Br-cAMP and 8-Br-cGMP had a considerably better solvolytic stability than the respective equatori al isomers as well as the DMNB-caged derivatives. Their usefulness for physiological studies was examined in a mammalian cell line expressin g the cyclic nucleotide-gated (CNG) ion channel of bovine olfactory se nsory neurons. (C) 1998 Elsevier Science S.A.