Water-soluble Azobenzene Photoswitches for Controlling Biological Systems

Photoswitches are small molecules that reversibly change their shape and properties uponirradiation with light of different colors. Since these molecules can be manipulated with nonharmfullight from the outside at any given location and time, photoswitches are a powerfultool to study different biological targets and for the development of novel light-responsivetherapeutics. The major challenges for the application of photoswitches in biological settingare their insolubility in water as well as the fact that the aqueous environment often has anegative impact on the properties of the photoswitch. In addition, many known photoswitchesrespond to UV light which is damaging to tissue. Those challenges have inspired great effortsto redesign the photoswitch molecules to fully respond to exclusively visible light while alsofeaturing water solubility. In my thesis I focused on developing water-soluble photoswitchesand applying them to manipulate biological systems. The synthesized photoswitches wereused to harness the cell-destroying activity of a biological toxin resulting, in a system whichcould destroy cancer cells upon illumination with light of a specific color. Furthermore, aphotoswitch was incorporated into a peptide known to play a crucial role inneurodegenerative diseases, such as Huntington’s disease, to shed light on the mechanism ofthe disease. Furthermore, this thesis reports several photoswitches which are both watersolubleand completely responsive to visible light thus bringing them one step closer towardsapplications in living organisms.