Photoswitching – Light-reversible Pharmacological Activity

A widely used optically active tool in photopharmacology is a photoswitch. A photoswitch is a molecule that reversibly changes its chemical and/or optical properties upon light irradiation. Illumination with a certain wavelength leads to photoisomerization of the molecule into its active state, whereas light of a second wavelength relaxes the molecule back into its inactive ground state. Synthetic photoswitches such as azobenzene derivatives have previously been used to probe the kinetics of for example nicotinic receptors. This is made possible by the different pharmacological binding properties of the cis and trans stereoisomers of the molecule, respectively.

Apart from probing the activity of receptors, synthetic photoswitches can also be used to reversibly and remotely control a drug’s activity with high temporal precision at the desired site of action with a simple flash of light.

Up until now, photoswitching of pharmacologically active compounds has been applied to target not only transmembrane proteins (e.g. transporters, ion channels, G protein-coupled receptors) and soluble proteins (e.g. kinases, proteases), but also lipid membranes and even nucleic acids.

An impressive application of a newly developed benzimidazole photoswitch (OptoBI-1) has been achieved by our pxONE user family member Bernadett Bacsa and the team of Prof. Klaus Groschner. They accomplished fully light-reversible pharmacological control over the activity of the TRPC3 channel in T-lymphocytes.