Junior Research Group: ChemBioProbes (Johannes Broichhagen)

Probes for compartmentalized labelling

In a dynamic cellular environment, proteins move and reside in different compartments. Accordingly, ways have to be found to label the same proteins differently when they are not at locations. Tuning the SNAP-tag substrate BG to its sulfonated version SBG, fluorophores are endowed with an impermeable leaving group. Besides better solubility, no evaluation of the cargo is needed as it stays untouched; and as such, any desired fluorophore can be employed to only label the surface exposed pool of a protein. Showcasing this for a member of every G protein-coupled receptor (GPCR) class, we performed super resolution microscopy, protein tracking of turnover and stoichiometry measurements of different receptor pools.  

Enodogenous protein labelling

Attaching fluorophores to peptidic antagonists of GLP1R, a protein involved in glucose homeostasis and appetite regulation, we endowed this receptor in its native environment with a dye. As such, we are able to closely look where it resides in the cell, with ramifications for the understanding of protein dynamics and generation of specific markers for differentiated stem cells.

Photocontrolling GPCRs

 

G protein-coupled receptors are cell surface proteins that sense stimuli outside of the cell and translate this into an intracellular response. Albeit being the largest drug target, the activation mechanism and fine interplay remain partly understood. Using a combination of photoswitchable molecules with protein engineering, we are able to use light with its unique spatiotemporal resolution to remote- and precise-control metabotropic glutamate receptors, key players in health and disease in the nervous system. Recently, quantitative efficacy was achieved for the first time by increasing the valency of our photoswitches – a chemical trick that might be amenable to other targets.

 

Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10
13125 Berlin, Germany
+4930 94793 - 100 
+4930 94793 - 109 (Fax)
info(at)fmp-berlin.de

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