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Sensitizing DNA Towards Low‐Energy Electrons with 2‐Fluoroadenine
Authors:Jenny Rackwitz  Dr Janina Kopyra  Dr Iwona D?bkowska  Kenny Ebel  Milo? Lj Rankovi?  Prof?Dr Aleksandar R Milosavljevi?  Prof?Dr Ilko Bald
Institution:1. Institute of Chemistry—Physical Chemistry, University of Potsdam, Potsdam, Germany;2. Faculty of Sciences, Siedlce University, Siedlce, Poland;3. Department of Chemistry, University of Gdańsk, Gdańsk, Poland;4. Institute of Physics Belgrade, University of Belgrade, Belgrade, Serbia;5. SOLEIL, l'Orme des Merisiers, St. Aubin, BP48, 91192, Gif sur Yvette Cedex, France;6. Department 1—Analytical Chemistry and Reference Materials, BAM Federal Institute for Materials Research and Testing, Berlin, Germany
Abstract:2‐Fluoroadenine (2FA) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low‐energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in 2FA are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion‐mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in 2FA‐containing oligonucleotides upon irradiation with LEEs. The incorporation of 2FA into DNA results in an enhanced strand breakage. The strand‐break cross sections are clearly energy dependent, whereas the strand‐break enhancements by 2FA at 5.5, 10, and 15 eV are very similar. Thus, 2FA can be considered an effective radiosensitizer operative at a wide range of electron energies.
Keywords:ab initio calculations  dissociative electron attachment  DNA origami  DNA radiation damage  fludarabine
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