TY - JOUR A1 - Kopyra, J. A1 - Keller, A. A1 - Bald, Ilko T1 - On the role of fluoro-substituted nucleosides in DNA radiosensitization for tumor radiation therapy JF - RSC Advances N2 - Gemcitabine (2',2'-difluorocytidine) is a well-known radiosensitizer routinely applied in concomitant chemoradiotherapy. During irradiation of biological media with high-energy radiation secondary low-energy (<10 eV) electrons are produced that can directly induce chemical bond breakage in DNA by dissociative electron attachment (DEA). Here, we investigate and compare DEA to the three molecules 2'-deoxycytidine, 2'-deoxy-5-fluorocytidine, and gemcitabine. Fluorination at specific molecular sites, i.e., nucleobase or sugar moiety, is found to control electron attachment and subsequent dissociation pathways. The presence of two fluorine atoms at the sugar ring results in more efficient electron attachment to the sugar moiety and subsequent bond cleavage. For the formation of the dehydrogenated nucleobase anion, we obtain an enhancement factor of 2.8 upon fluorination of the sugar, whereas the enhancement factor is 5.5 when the nucleobase is fluorinated. The observed fragmentation reactions suggest enhanced DNA strand breakage induced by secondary electrons when gemcitabine is incorporated into DNA. KW - Dissociative electron attachment KW - DNA radiation damage KW - Gemcitabine KW - DNA radiosensitizer KW - Tumor radiation therapy PY - 2014 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-302872 DO - https://doi.org/10.1039/c3ra46735j SN - 2046-2069 VL - 4 IS - 13 SP - 6825 EP - 6829 PB - RSC Publishing CY - London AN - OPUS4-30287 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bald, Ilko A1 - Keller, A. T1 - Molecular processes studied at a single-molecule level using DNA origami nanostructures and atomic force microscopy JF - Molecules N2 - DNA origami nanostructures allow for the arrangement of different functionalities such as proteins, specific DNA structures, nanoparticles, and various chemical modifications with unprecedented precision. The arranged functional entities can be visualized by atomic force microscopy (AFM) which enables the study of molecular processes at a single-molecular level. Examples comprise the investigation of chemical reactions, electron-induced bond breaking, enzymatic binding and cleavage events, and conformational transitions in DNA. In this paper, we provide an overview of the advances achieved in the field of single-molecule investigations by applying atomic force microscopy to functionalized DNA origami substrates. KW - DNA origami KW - atomic force microscopy KW - single-molecule analysis KW - DNA radiation damage KW - protein binding KW - enzyme reactions KW - G quadruplexes PY - 2014 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-314343 DO - https://doi.org/10.3390/molecules190913803 SN - 1420-3049 VL - 19 IS - 9 SP - 13803 EP - 13823 PB - MDPI CY - Basel AN - OPUS4-31434 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -