In this research line we develop advanced chemical biology tools for precision regulation of biological processes. Our first approach delivered blue light control over the cell cycle and apoptosis of cancer cells in collaboration with the Zanin lab. To this end we have photocaged the versatile proteasome inhibitor MG132 directly at its reactive aldehyde function keeping the oxidation state unchanged. Upon caging bioactivity is lost and cells proliferate normally. Irradiation releases the inhibitor at a given time and leads to metaphase arrest of the cells. Prolonged exposure causes the apoptosis pathway to be activated and blue light treated cells die. Our light-activated biomolecular tool therefore enables spatial-temporal control of cell fate and was further shown to be compatible with live-cell imaging methods.1
In a second approach we use the reversible photoresponse of indigoid chromophores to modulate inhibition of enzymes vital for cell survival. Rhodanine-based chromophores are ubiquitous molecular structures in different applied fields of chemistry ranging from materials to solar cells and bioactive compounds. We have demonstrated how photoswitching can be elevated to high performance and how rhodanines can be used as advanced photopharmacology tools. In this regard we showed that a known inhibitor of PIM-1 kinase can be strongly photomodulated in its activity allowing for light-controlled apoptosis induction in cancer cells. We also found new derivatives as candidates for potent PIM-1 kinase inhibitors.2
