My project focuses on the development of novel photopharmacology agents as anticancer drug candidates. These agents shall be modified with chemical moieties allowing the fluorescence readout to help in structure-activity relationship (SAR) studies and in the mechanism-of-action (MoA) investigations. This feature will support pharmacokinetics (PK) characterization of my substances and make easier photopharmacological therapy optimization on the cellular, tissue, and whole-organism levels. I continue exploring the application of diarylethene-based photoswitches (DAE) in the backbones of the cyclic bioactive peptides (Figure 1). This approach has been pioneered at KIT by Dr. O. Babii, who developed a range of antimicrobial and oncolytic photopharmacology agents based on a decameric cyclic β-hairpin scaffold of antimicrobial peptide     Gramicidin S and of Dr. T. Schober, who recently used DAE in fluorescently-labeled photoswitchable cyclic arginine-rich cell-penetrating peptides.

In my Ph.D. project, I combine both approaches (DAE in a cyclic bioactive peptide, and fluorescence labeling) and select as the main target a different to GS parent peptide, Gymnopeptide A (Figure 2), which had been reported to possess anticancer activities in the nanomolar range.