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- W2790282010 abstract "Nowadays, one of the leading causes of death is cancer and its common way of treatment is photo- or radiotherapy. To increase the efficiency of these modalities one usually uses sensitizers that make cancer cell more sensitive to UV or ionizing radiation. Modified nucleosides with high electron affinity (EA), prone to dissociative electron attachment are the examples of such compounds. Irradiation of DNA modified with the radiosensitizing nucleosides with increased EA leads to the production of radicals. These radicals are believed to induce further DNA damage after hydrogen abstraction from the sugar moiety. While the first step of damage to the modified DNA - a nucleobase radical production - seems to be understood sufficiently well, the following degradation steps - i.e. hydrogen abstraction and further reactions resulting in a “fixed” damage require further studies. However, in order to test new radiosensitizers or understand the DNA degradation pathways models mimicking the native DNA environment are necessary. Indeed, in the cell nucleus DNA - a molecular target of radio- or phototherapy - interacts with a number of proteins. Thus, access to specific DNA-protein complexes, seem to be necessary to fully comprehend the sensitization processes. Here, we will present how a complex of the BrdG/BrdA/BrdC or BrdU-labeled dsDNA with a covalently linked peptide (dsDNA-PEP) can mimic the sensitized DNA in its native environment and serve as a tool for the development of radio- or photosensitizers. Labeled dsDNA-PEP radiolytes and photolytes were fully characterized using the LC-MS method. Moreover, the electron affinities (AEA) and circular dichroism (CD) spectra of the labeled oligonucleotides were calculated and measured. In summary, the obtained theoretical and experimental data allowed us to better understand the processes involved in the photo- and radio-damage of DNA in a well-defined model system." @default.
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- W2790282010 date "2018-02-01" @default.
- W2790282010 modified "2023-10-14" @default.
- W2790282010 title "Sensitized dsDNA-Peptide Complex and its Physicochemical Properties" @default.
- W2790282010 doi "https://doi.org/10.1016/j.bpj.2017.11.2427" @default.
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