Structure-based photopharmacology
The goal of this project is to use a photopharmacology approach to control antibiotic activity with light to achieve high precision activation and auto-deactivation to avoid environmental contamination of active ingredient and resistance build–up. Using a combination of synthetic, photochemical and cell biology methods various light-switches will be incorporated into antibiotics, their photoresponsive behavior studied and the modulation of biological activity tested. A similar approach will be followed for switchable quorum sensing molecules to control bacterial communication and biofilm formation with light.
Major challenges to be addressed in this PhD project include the design of switchable antibiotics with visible / near–IR photoswitching. This is an essential feature for deep tissue penetration in future clinical applications. Specifically, we focus on using modified azo-benzenes and novel photoswitches with extended conjugation. The novel photoswitches will also be incorporated in a selected series of bacterial quorum sensing molecules to control bacterial aggregation and biofilm formation.
Department: Stratingh Institute for Chemistry, RUG
Principal investigator(s): Prof. Dr. Ben Feringa
Publications
Kobauri, P., Szymanski, W., Cao, F., Thallmair, S., Marrink, S. J., Witte, M. D., Dekker, F. J., & Feringa, B. L. (2021). Biaryl sulfonamides as cisoid azosteres for photopharmacology [10.1039/D1CC00950H]. Chemical Communications, 57(34), 4126-4129. https://doi.org/10.1039/D1CC00950H
Kolarski, D., Miller, S., Oshima, T., Nagai, Y., Aoki, Y., Kobauri, P., Srivastava, A., Sugiyama, A., Amaike, K., Sato, A., Tama, F., Szymanski, W., Feringa, B. L., Itami, K., & Hirota, T. (2021). Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock. Journal of the American Chemical Society, 143(4), 2078-2087. https://doi.org/10.1021/jacs.0c12280
Lauxen, A. I., Kobauri, P., Wegener, M., Hansen, M. J., Galenkamp, N. S., Maglia, G., Szymanski, W., Feringa, B. L., & Kuipers, O. P. (2021). Mechanism of Resistance Development in E. coli against TCAT, a Trimethoprim-Based Photoswitchable Antibiotic. Pharmaceuticals, 14(5), 392. https://www.mdpi.com/1424-8247/14/5/392
Simeth, N. A., Kobayashi, S., Kobauri, P., Crespi, S., Szymanski, W., Nakatani, K., Dohno, C., & Feringa, B. L. (2021). Rational design of a photoswitchable DNA glue enabling high regulatory function and supramolecular chirality transfer [10.1039/D1SC02194J]. Chemical Science, 12(26), 9207-9220. https://doi.org/10.1039/D1SC02194J
Hoorens, M. W. H., Ourailidou, M. E., Rodat, T., van der Wouden, P. E., Kobauri, P., Kriegs, M., Peifer, C., Feringa, B. L., Dekker, F. J., & Szymanski, W. (2019). Light-controlled inhibition of BRAFV600E kinase. European Journal of Medicinal Chemistry, 179, 133-146. https://doi.org/10.1016/j.ejmech.2019.06.042
Hansen, M. J., Feringa, F. M., Kobauri, P., Szymanski, W., Medema, R. H., & Feringa, B. L. (2018). Photoactivation of MDM2 Inhibitors: Controlling Protein–Protein Interaction with Light. Journal of the American Chemical Society, 140(41), 13136-13141. https://doi.org/10.1021/jacs.8b04870
