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Photopharmacology: Towards Light-Controlled Therapy

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Current pharmacological treatments relay on using bioactive compounds that evoke a response by interacting with molecular targets in the human body. The selectivity of this interaction is crucial and the lack of it leads to the emergence of severe side-effects in the body and toxicity in the environment.

To solve this problem, drugs could be introduced whose activity could be reversibly or irreversibly turned on with light. The aim of this presentation is to describe the emerging concept of photopharmacology,[1] which is currently being developed and applied to precisely control the activity of drugs using light. Light offers unparalleled advantages in regulation of bioactivity and as an input/output signal in medical (mostly optical/optoacoustic) imaging. Combination of those two paradigms along the principles of theranostics requires light-responsive tools that empower both therapy and imaging.

The talk will focus on our efforts towards bridging light and medicine, focusing first on new light-operated tools2 (molecular photoswitches[3,4,5] and photocages6. Next, I will highlight the synergies between medical imaging and therapy, offered by light, through photoresponsive optical7 and magnetic resonance[8,9] imaging agents. The examples of light-controlled bioactive molecules presented will include small molecules10 and proteins11. Finally, using those examples, I will discuss the structural aspects12 and design principles13 in photopharmacology.

References: [1] M. W. H. Hoorens et al. Trends. Biochem. Sci. 43, 567 (2018); [2] I. M. Welleman et al. Chem. Sci. 11, 11672-11691 (2020); [3] L. N. Lameijer et al. Angew. Chem. Int. Ed. 59, 21663-21670 (2020); [4] M. W. H. Hoorens et al. Nature Comm. 10, 2390 (2019); [5] M. W. H. Hoorens et al. Chem. Sci. 12, 4588-4898 (2021); [6] K. Sitkowska et al. ChemComm, 56, 5480-5483 (2020); [7] F. Reebing et al. ACS Omega 5, 22071-22080 (2020); [8] F. Reebing et al. Curr. Opin. Biotech. 58, 9 (2019) [9] F. Reebing et al. Chem. Comm. 55, 10784 (2019); [10] D. Kolarski et al. Nat. Commun. ASAP (2021); [11] N. Mutter et al. J. Am. Chem. Soc. 141, 14356 (2019); [12] V. Arkhipova et al. J. Am. Chem. Soc., 143, 1513–1520 (2021); [13] D. Kolarski et al. Org. Biomol. Chem. 19, 2312 – 2321 (2021).

This talk is part of the Biophysical Seminars series.

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