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Protein Photocontrol: Beyond Microtubules

Photopharmaceuticals can be reversibly controlled with excellent temporal precision. This generally recommends them as reagents for studying inherantly rapid-response systems with inbuilt switch-off kinetics, including signal integration and cascade transmission systems in biology. The challenge is to create photopharmaceuticals with sufficient biochemical specificity, potency, and robustness (repeatability of action / solubility / ease of transfer between model systems). Building on our experience in microtubule photocontrol, we have entered other target spaces with new challenges and opportunities:

(A) TRP channels form a family of 28 ion channels, playing prime roles in sensory integration of simultaneous signal inputs (temperature, pH, chemical ligands, etc) as well in the bulk mineral transport (homeostasis) needed for cell survival and replication. Kickstarted by the DFG Transregio SFB152 TRiPs to Homeostasis we are working on new photopharmaceutical modulators of TRP channels, for high-temporal-precision studies of their functional roles in vitro and in vivo. As high-impact sensory and signaling systems that can be exquisitely primed for chemical intervention, TRPs offer photopharmacologist fertile grounds for methodological explorations far beyond the current paradigms of "switching a blocker more-on and more-off". For an excellent introduction to sensory receptor modulation, see Colquhoun 1998.

BTDAzo: the first TRPC5-selective photoswitchable modulator, applied from cell culture to tissue slice investigations (Angewandte 2022) 26E01: a novel, selective, nontoxic blocker for TRPV3 (Cell Calcium 2020)

(B) Target-based Collaborations: we collaborate to develop photoresponsive bioactive tool compounds for various cellular target systems as opportunities arise.

MRORs: the first photoswitchable modulators of nuclear hormone receptor RORĪ³
(ChemRxiv 2023; with the Merk group)
neo-optojasps: self-switch-off (fast-relaxing) photoswitchable actin cytoskeleton inhibitors
(Angewandte 2022; with the Trauner and Arndt groups)
optojasps: first-in-class photoswitchable actin cytoskeleton inhibitors
(JACS 2020; with the Arndt and Trauner groups)