caged-Ins(145)P3 / PM

Membrane-permeant derivatives of inositol polyphosphates and phosphoinositides require the intracellular enzymatic hydrolysis of several protecting groups. for instance of acyloxymethyl esters. in order to generate the biologically active compound. The highly complicated kinetics of these biochemical steps may lead to unphysiological effects. The physiological signal usually appears to be very rapid. The photolysis of membrane-permeant caged derivatives of Ins(1.4.5)P3 and other inositol polyphosphates might mimic fast intracellular responses. In an initial step cells are loaded with the caged Ins(1.4.5)P3 derivative. Within 30 to 180 minutes all bioactivatable protecting groups remove. generating caged inositol polyphosphate. The cage is known to prevent biological activity when placed at the right position. in this case the 6-hydroxygroup. The photochemical destruction of the cage (360-400nm) releases active Ins(1.4.5)P3 within a few seconds. thus mimicking the rapid responses of the receptor/phospholipase C signaling system in the cell. Since this approach does not (directly) trigger other signaling events. for instance PKC activation after receptor-mediated diacylglycerol (DAG) formation. membrane-permeant derivatives of signaling molecules are able to help dissecting signaling pathways.