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Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen‐Dependent Photodynamic Cancer Therapy |
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| Authors: | Dr. Oleg Babii Dr. Sergii Afonin Prof. Liudmyla V. Garmanchuk Dr. Viktoria V. Nikulina Tetiana V. Nikolaienko Olha V. Storozhuk Dmytro V. Shelest Dr. Olga I. Dasyukevich Prof. Liudmyla I. Ostapchenko Dr. Volodymyr Iurchenko Dr. Sergey Zozulya Prof. Anne S. Ulrich Prof. Igor V. Komarov |
| Affiliation: | 1. Institute of Organic Chemistry (IOC), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany;2. Institute of Biological Interfaces (IBG-2), KIT, Karlsruhe, Germany;3. Institute of Biology, TSNUK, Kyiv, Ukraine;4. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine (NASU), Kyiv, Ukraine;5. Enamine Ltd., Kyiv, Ukraine;6. Institute of High Technologies (IHT), Taras Shevchenko National University of Kyiv (TSNUK), Kyiv, Ukraine |
| Abstract: | Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene‐derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light‐sensitive molecule is not a mediator but is itself the cytotoxic agent. As a derivative of the cyclic amphiphilic peptide gramicidin S, the peptidomimetic exists in two thermally stable photoforms that are interconvertible by light of different wavelengths. The isomer generated by visible light shows much stronger toxicity against tumor cells than the UV‐generated isomer. First in vivo applications are demonstrated on a tumor animal model to illustrate how the peptidomimetic can be administered in the less toxic form and then activated locally in a solid tumor by visible light. |
| Keywords: | cancer drug design peptidomimetics photoswitches photodynamic therapy |