DMACM-Caged Adenosine Nucleotides: Ultrafast Phototriggers for ATP, ADP, and AMP Activated by Long-Wavelength Irradiation

The development of new photocleavable adenosine nucleotides based on the photochemistry of [7-(dimethylamino)coumarin-4-yl]methyl (DMACM) esters is described. The phototriggers liberate adenosine triphosphate (ATP), diphosphate, and monophosphate upon UV/Vis irradiation between 334 and 405 nm. The efficiency of photocleavage at long wavelengths is high as a result of a combination of appropriate quantum yields and intensive absorptivities. By using time-resolved fluorescence spectroscopy, we determined a lower limit of 1.6×10⁹ s⁻¹ for the rate constant of the release of ATP from DMACM-caged ATP. The favorable properties of DMACM-caged ATP were confirmed in physiological studies by confocal laser scanning microscopy. We were able to uncage DMACM-caged ATP in cultures of mouse astrocytes and in brain tissue slices from mice and were also able to measure the effect of photoreleased ATP on the cellular response of astrocytes, namely the ability of the ATP to evoke Ca²⁺ ion waves.