Toward the Development of New Photolabile Protecting Groups That Can Rapidly Release Bioactive Compounds upon Photolysis with Visible Light

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Abstract
The synthesis and characterization of a new photolabile protecting group (caging group) for carboxylic acids, the 2-(dimethylamino)-5-nitrophenyl (DANP) group, is described. This compound has a major absorption band in the visible wavelength region with a maximum near 400 nm (ε400 = 9077 M-1 cm-1 at pH 7.4 and 21 °C). The caging group is attached through an ester linkage to the carboxyl functionality of β-alanine, which activates the inhibitory glycine receptor in the mammalian central nervous system. Such caged compounds play an important role in transient kinetic investigations of fast cellular processes. Upon photolysis of DANP-caged β-alanine, the caging group is released within 5 μs. Quantum yields of 0.03 and 0.002 were obtained in the UV region (308 and 360 nm) and the visible region (450 nm), respectively. Laser-pulse photolysis experiments, using 337 or 360 nm light, were performed with the caged compound equilibrated with HEK 293 cells transiently transfected with cDNA encoding the α1 homomeric, wild-type glycine receptor. The experiments demonstrated that neither DANP-caged β-alanine nor its byproducts inhibit or activate the glycine receptors on the cell surface. Under physiological conditions, the DANP-caged β-alanine is water-soluble and stable and can be used for transient kinetic measurements.