Caged cAMP

Furuta, T., Momotake, A., Sugimoto, M., Hatayama, M., Torigai, H. and Iwamura, M. (1996) Acyloxycoumarinylmethyl-caged cAMP, the photolabile and membrane-permeable derivative of cAMP that effectively stimulates pigment-dispersion response of melanophores. Biochemical and Biophysical Research Communications, 228, 193-198. 

Caged cAMP has been particularly useful in neuroscience to decouple the neuron response to the natural neuronal stimulation by bypassing the activation of the pathway, especially for olfactory transduction [20,21] or for axon guidance during the establishment of a neural map [22]. 

Prepare a 1-mM stock solution of DMNB-caged cAMP in dimethylsulfoxide (DMSO). Keep frozen at -20°C and protect from light. Prepare a 10-pM dilution in phosphate buffer for the experiment. 

Set the pump to a pumping rate of 5 pL/h, and start the flow of caged cAMP. This corresponds to a flow speed of about 110 pm/s for the given channel dimensions (wNote... 

The single-cell measurements are started at the far end of the channel close to the outlet. Work your way up toward the inlet through which the caged cAMP solution is infused. In this way, it can be ensured that a chosen cell has not been hit by the cAMP release of a previous stimulation experiment. 

Caged cAMP R = Acetyl R = Propionyl R = Hydroxy R = Methoxy... 

Morris Hubert about Buchenwald, acc. to Ari L. Goldman, Time Too Painful to Remember , New York Times, November 10, 1988 7n the camp there was a cage with a bear and an eagle, he said. Every day, they would throw a Jew in there. The bear would tear him apart and the eagle would pick at his bones. ... 

The synthesis of two novel caged compounds, 4,5-dimethoxy-2-nitrobenzyl 8-bromo-cAMP (caged 8-Br-cAMP) (76) and 4,5-dimethoxy-2-nitrobenzyl 8-bromo-cGMP (caged 8-Br-cGMP) (77) by reaction of the respective cyclic... 

Figure 15.4 Examples of caged compounds and other photoactivatable drugs, (a) and (b) on photolysis the o-nitrobenzyl protecting group detaches and releases ATP and cAMP, respectively (c) photosensitive chelator. The cis form of the molecule binds Zn2+ but the trans form does not (d) frequently used photosensitive calcium chelators. Nitr-2 (R = CH3), Nitr-5 (R = H) (e) ICYP-diazirine, a photoaffinity reagent that becomes covalently attached to p-adrenergic receptors upon photolysis.

When REFs were exposed to the membrane-permeant PKA activator, 8-(4-chlorophenylthio)-cAMP (CPT-cAMP), they underwent the same morphological transformation as described above (disruption of actin stress fibers leading to cell shape changes). In contrast, cells microinjected with the caged peptide (5 pM estimated intracellular concentration) and exposed to UV irradiation were unable to respond to the CPT-cAMP stimulus, demonstrating that the CPT-cAMP activation of the PKA pathway had been efficiently blocked in vivo by the decaged peptide [152],... 

One of the prime assets of photolability is the opportunity to release latent biologically active agents in vivo by simple irradiation of a protected (caged) precursor. A synthesis of inhibitors of cAMP-dependent protein kinase (PKA) illustrates the point. The arginine (Arg) in the nonapeptide Gly-Arg-Thr-Gly-Arg-Arg-Asn-... 

The successful introduction of o-nitrobenzyl caged ATP into physiological media instigated interest in expanding the applications of caged release to a wide variety of biochemical systems. The list includes the mechanism of release of P in skeletal muscle, the function of cAMP in the relaxation of distal muscle, the ATP-induced mechanism of actomyosin in muscle contraction, and the activation of antitumor antibiotics to highly reactive pyrrolic-type intermediates responsible for DNA crosslinking reactions. " ... 

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