[7-(Dialkylamino)coumarin-4-yl]methyl-Caged
Compounds as Ultrafast and Effective Long-Wavelength Phototriggers of
8Bromo-Substituted Cyclic Nucleotides.
Hagen V, Frings S, Wiesner B,
Helm S, Kaupp UB, Bendig J.
Forschungsinstitut fur Molekulare Pharmakologie Robert-Rossle-Strasse 10, 13125
Berlin, Germany, Fax: (+49) 30-9479-159.
[7-(Dimethylamino)coumarin-4-yl]methyl (DMACM) and
[7-(diethylamino)coumarin-4-yl]methyl (DEACM) esters of 8bromoadenosine
3',5'-cyclic monophosphate (8-Br-cAMP) and 8bromoguanosine 3',5'-cyclic
monophosphate (8-Br-cGMP) are described as novel caged compounds for
8bromo-substituted cyclic nucleotides. Synthesis is accomplished by
treatment of the free acids of the cyclic nucleotides with the corresponding
7(dialkylamino)-substituted 4(diazomethyl)coumarins. Irradiation of the DMACM-
and DEACM-caged cyclic nucleotides with UV light stimulates the release of the
cyclic nucleotides within roughly a nanosecond. The new caged compounds are
resistant to hydrolysis in aqueous buffers and exhibit long-wavelength
absorption properties with maxima at 400 nm, high extinction coefficients, and
high quantum yields (0.15-0.31). Their favorable properties render these
compounds the most efficient and rapid phototriggers of 8bromo-substituted cyclic
nucleotides known. The usefulness of the compounds for physiological studies
under nondamaging light conditions was examined in HEK293 cells expressing the
alpha subunit of the cyclic-nucleotide-gated (CNG) channel of cone
photoreceptors (CNGA3) and of olfactory neurons (CNGA2) by using confocal laser
scanning microscopy and the patch clamp technique.
Chembiochem 2003 May 9;4(5):434-42