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[7‐(Dialkylamino)coumarin‐4‐yl]methyl‐Caged Compounds as Ultrafast and Effective Long‐Wavelength Phototriggers of 8Bromo‐Substituted Cyclic Nucleotides
Author(s) -
Hagen Volker,
Frings Stephan,
Wiesner Burkhard,
Helm Siegrun,
Kaupp U. Benjamin,
Bendig Jürgen
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200300561
Subject(s) - nucleotide , chemistry , coumarin , cyclic nucleotide , stereochemistry , photochemistry , biochemistry , organic chemistry , gene
[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 α 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.