A ChemBio Toolbox to Enlighten Biological Processes

Life is highly dynamic relaying on a myriad of carefully orchestrated processes with strict spatial and temporal control. To decipher cellular functions and, in turn, address complex biological questions is necessary to have precise control. In my group, we pursue such the dream of achieving a molecularly precise understanding of biology to address the problems arising from misregulation. For this purpose, we focus on the design of innovative chemical biology tools. In particular, optochemical tools based on the synthesis of photosensitive molecules such as fluorophores, photosensitizers and photoswitches enabled us the desired conditional modulation in disease-related processes. In this talk I will make a brief summary about our projects where fluorophores have demonstrated the possibility of efficiently labelled multidrug resistant bacteria1; the development of bioorthogonally activatable photosensitizers for photodynamic therapy2-3 and the use of photoswitches for light-controllable gene expression, 4-8

References

1. Schulte, L. N.; Heinrich, B.; Janga, H.; Schmeck, B. T.; Vazquez, O., A Far-Red Fluorescent DNA Binder for Interaction Studies of Live Multidrug-Resistant Pathogens and Host Cells. Angew Chem Int Ed Engl 2018, 57 (36), 11564-11568.

2. Linden, G.; Zhang, L.; Pieck, F.; Linne, U.; Kosenkov, D.; Tonner, R.; Vazquez, O., Conditional Singlet Oxygen Generation through a Bioorthogonal DNA-targeted Tetrazine Reaction. Angew Chem Int Ed Engl 2019, 58 (37), 12868-12873.

3. Linden, G.; Vazquez, O., Bioorthogonal Turn-On BODIPY-Peptide Photosensitizers for Tailored Photodynamic Therapy. Chemistry 2020, 26(44), 10014-10023.

4. Albert, L.; Xu, J.; Wan, R.; Srinivasan, V.; Dou, Y.; Vazquez, O., Controlled inhibition of methyltransferases using photoswitchable peptidomimetics: towards an epigenetic regulation of leukemia. Chem Sci 2017, 8 (6), 4612-4618.

5. Heinrich, B.; Bouazoune, K.; Wojcik, M.; Bakowsky, U.; Vazquez, O., ortho-Fluoroazobenzene derivatives as DNA intercalators for photocontrol of DNA and nucleosome binding by visible light. Org Biomol Chem 2019, 17 (7), 1827-1833.

6. Albert, L.; Penalver, A.; Djokovic, N.; Werel, L.; Hoffarth, M.; Ruzic, D.; Xu, J.; Essen, L. O.; Nikolic, K.; Dou, Y.; Vazquez, O., Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches. Chembiochem 2019, 20 (11), 1417-1429.

7. Albert, L.; Nagpal, J.; Steinchen, W.; Zhang, L.; Werel, L.; Djokovic, N.; Ruzic, D.; Hoffarth, M.; Xu, J.; Kaspareit, J.; Abendroth, F.; Royant, A.; Bange, G.; Nikolic, K.; Ryu, S.; Dou, Y.; Essen, L. O.; Vazquez, O., Bistable Photoswitch Allows in Vivo Control of Hematopoiesis. ACS Cent Sci 2022, 8 (1), 57-66.

8. Zhang, L.; Xie, X.; Djokovic, N.; Nikolic, K.; Kosenkov, D.; Abendroth, F.; Vazquez, O., Reversible Control of RNA Splicing by Photoswitchable Small Molecules. J Am Chem Soc 2023, 145 (23), 12783-12792.