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XVIII - Lang/Sumser/Thorn-Seshold

Photo/photoredox-switchable ligands as chemical tools for optogenetics



1) Kathrin Lang (PI; Technical University Munich), coworker:

2) Martin Sumser (PI; Ludwig-Maximilians-University Munich), coworker:

3) Oliver Thorn-Seshold (PI; Ludwig-Maximilians-University Munich), coworker:



Synthetic small-molecule reagents that are photoswitchable ligands for proteins of interest (“photopharmaceuticals”) have greatly extended the reach and spatiotemporal precision of pharmacological manipulations. However, the azobenzene molecular scaffolds used as the basis for most photoswitchable ligands usually have only a narrow photoreversibility index, with typically ca. 5-fold dynamic range. Therefore, this approach has experienced several difficulties transitioning from cell-free proof-of-principle, to cell or in vivo biological research use in general.
SPP1926 project XVIII aims to deliver a new molecular concept for photopharmaceutical and especially optochemical genetics studies, with a photoreversibility dynamic range of ca. 100-fold. This wider dynamic range will enable tools based on this concept to be applied more broadly and more reliably than existing techniques. We will translate this concept to intracellular applications by installing highly specific bioorthogonally reactive motifs on key proteins using genetic code expansion. Lastly we will examine this concept for artificial photosensitisation of endogenous ion channels, in the context of vision restoration.