Novel molecular photoswitches for use in chemical biology

Photoswitchable compounds, which can be reversibly switched between two isomers by light, continue to attract significant attention for a wide array of applications that capitalise on the high temporal and spatial precision of using light as a stimulus. The recently established field of photopharmacology uses photoswitchable ligands that are selective for a specific cellular target, such as a receptor or an enzyme, and are employed as therapeutic entities. These ligands undergo a change in shape, flexibility, or electronic properties upon irradiation with light that leads to a change in the affinity for their cellular target; therefore, they exhibit a light-dependent therapeutic activity. lding on our recent work on novel molecular photoswitches (J. Am. Chem. Soc. 2014, 136, 11878; J. Am. Chem. Soc. 2017, 139, 1261) and their applications (Chem. Commun. 2016, 52, 4521; ACS Infect. Dis. 2017, 3, 152) this project will seek to explore new design strategies to access photoswitchable molecules with improved performance and additional functionality. Application of these photoswitches to novel approaches in chemical biology, particularly in the area of photopharmacology, will be explored. The research area for this project is Chemical biology and biological chemistry.
Azoheteroarenes represent a relatively new but understudied type of photoswitch, where one or both of the aryl rings from the conventional azobenzene class has been replaced with a five-membered heteroaromatic ring. Within this class, our group recently discovered the arylazopyrazoles, which offer quantitative photoswitching and high thermal stability of the Z isomer (half-lives of up to about 1000 days). We have developed excellent understanding of the structure-property relationships for a wide array of comparable azoheteroaryl photoswitches and are now placed to explore these state-of-the-art systems for photopharmacology applications. This proposal will seek to develop photopharmacological agents and improved designs for biological application. A range of targets will be explored, from membrane channels to protein-protein interactions.

Strategic Themes: Healthcare Technologies; Physical Sciences
Research Areas: Analytical science; Physical Sciences: Chemical Biology and Biological Chemistry