| Autor: |
Babii O; Institute of Biological Interfaces (IBG-2) , Karlsruhe Institute of Technology (KIT) , POB 3640, 76021 Karlsruhe , Germany., Afonin S; Institute of Biological Interfaces (IBG-2) , Karlsruhe Institute of Technology (KIT) , POB 3640, 76021 Karlsruhe , Germany., Ishchenko AY; Institute of High Technologies , Taras Shevchenko National University of Kyiv , Vul. Volodymyrska 60 , 01601 Kyiv , Ukraine.; Enamine Ltd. , Vul. Chervonotkatska 78 , 02066 Kyiv , Ukraine., Schober T; Institute of Organic Chemistry (IOC) , Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6 , 76131 Karlsruhe , Germany., Negelia AO; Institute of Biology and Medicine , Taras Shevchenko National University of Kyiv , Prosp. Hlushkova 2 , 03022 Kyiv , Ukraine., Tolstanova GM; Institute of Biology and Medicine , Taras Shevchenko National University of Kyiv , Prosp. Hlushkova 2 , 03022 Kyiv , Ukraine., Garmanchuk LV; Institute of Biology and Medicine , Taras Shevchenko National University of Kyiv , Prosp. Hlushkova 2 , 03022 Kyiv , Ukraine., Ostapchenko LI; Institute of Biology and Medicine , Taras Shevchenko National University of Kyiv , Prosp. Hlushkova 2 , 03022 Kyiv , Ukraine., Komarov IV; Institute of High Technologies , Taras Shevchenko National University of Kyiv , Vul. Volodymyrska 60 , 01601 Kyiv , Ukraine.; Enamine Ltd. , Vul. Chervonotkatska 78 , 02066 Kyiv , Ukraine.; Lumobiotics GmbH , Auerstraße 2 , 76227 Karlsruhe , Germany., Ulrich AS; Institute of Biological Interfaces (IBG-2) , Karlsruhe Institute of Technology (KIT) , POB 3640, 76021 Karlsruhe , Germany.; Institute of Organic Chemistry (IOC) , Karlsruhe Institute of Technology (KIT) , Fritz-Haber-Weg 6 , 76131 Karlsruhe , Germany. |
| Abstrakt: |
Five series (28 structures) of photoswitchable β-hairpin peptides were synthesized based on the cyclic scaffold of the natural antibiotic gramicidin S. Cell-type selectivity was compared for all activated (diarylethene "ring-open") and deactivated ("ring-closed") forms in terms of antibacterial activity (MIC against Escherichia coli and Bacillus subtilis), anticancer activity (IC 50 against HeLa cell line), and hemolytic cytotoxicity (HC 50 against human erythrocytes). Correlations between the conformational plasticity of the peptides, their hydrophobicity, and their bioactivity were also analyzed. Considerable improvements in selectivity were achieved compared to the reference compound. We found a dissociation of the anticancer activity from hemolysis. Phototherapeutic indices (PTI), HC 50 (closed)/MIC(open) and HC 50 (closed)/IC 50 (open), were introduced for the peptides as safety criteria. The highest PTI for HeLa-selective toxicity were observed among analogues containing hydroxyleucine on the hydrophobic face. For one compound, high PTIs were demonstrated across a range of different cancer cell lines, including a doxorubicin-resistant one. |
