Controlling cell chemistry with caged compounds.

Abstract

compounds are artificial molecules whose biological actIvity is controlled by light, usually by photolytic conversion from an inactive to an active form. The term caged has become popular because it is brief and pictorial, not because it is accurate. It is based on an early concept that small biologically active species might in general be trapped inside a large framework that would be opened or dismembered upon illumination, thus uncaging the contents. In fact, total imprisonment of one molecule by another so that the contents cannot exchange with the outside world has only recently been accomplished (19, 29), and controlled photochemical disruption of the cage is difficult or impossible. In nearly all successful caged molecules so far, simple covalent bond formation masks some feature important for biological recognition. Photochemical cleavage of that single bond releases the active species. Caged compounds are biologically useful because illumination can be so easily controlled in timing, location, and amplitude. Therefore abrupt or localized changes in concentration of active species can be generated with controlled amplitudes. This capability is particularly valuable when rapid mechanical mixing is impractical, for example inside a more-or-Iess intact cell, tissue, or protein crystal, or when microscopic spatial gradients are desired. Photolysis of caged compounds is one of the best techniques to examine the fast kinetics or spatial heterogeneity of biochemical responses in