Sensitizing DNA Towards Low‐Energy Electrons with 2‐Fluoroadenine

Abstract

2-Fluoroadenine ((2F) A) 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 (2F) A 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 (2F) A-containing oligonucleotides upon irradiation with LEEs. The incorporation of (2F) A into DNA results in an enhanced strand breakage. The strand-break cross sections are clearly energy dependent, whereas the strand-break enhancements by (2F) A at 5.5, 10, and 15 eV are very similar. Thus, (2F) A can be considered an effective radiosensitizer operative at a wide range of electron energies.

Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low‐Energy Electrons (0.5–9 eV)

“…However, there are strict limitations concerning the length of the oligonucleotides that can be used in such experiments. By using DNA origami structures, these limitations can be overcome, and the absolute strand break cross‐sections of tailored target sequences can be determined . Electron‐energy‐dependent measurements aimed at revealing the resonant character of the LEE‐induced strand breakage with oligonucleotides have not been performed thus far with the DNA origami technique, even though it remains a critical task to evaluate previous studies based on the use of plasmid DNA and also to study the influence of sequence modifications on the DEA resonances.…”

“…Herein, we report on the energy dependence of DNA strand breaks in single‐stranded oligonucleotides by using the established DNA origami technique and elucidate the influence of the potential radiosensitizer 8‐bromoadenine ( 8Br A) on the absolute strand break (SB) cross‐section. The data are supported by DEA measurements performed with the isolated molecule 8Br A in the gas phase.…”

Resonante Bildung von Strangbrüchen in sensibilisierten Oligonukleotiden induziert durch niederenergetische Elektronen (0.5–9.0 eV)

“…DEA tritt bei spezifischen Energien auf und führt zu resonanten Strukturen in den Wirkungsquerschnitten von Einzelstrangbrüchen (ESBs) und Doppelstrangbrüchen (DSBs) . Für die Chemotherapeutika Cisplatin, Gemcitabin und 2‐Fluoradenin ( 2F A) wurde bereits gezeigt, dass sie den Schaden durch NEEs verstärken, wodurch sich ihre radiosensibilisierende Wirkung zumindest teilweise erklären lässt . Die Einsatzmöglichleiten von Plasmid‐DNA für Bestrahlungsexperimente ist jedoch begrenzt, da der Einfluss der DNA‐Sequenz, der DNA‐Konformation und der spezifischen Präparation unbekannt bleiben.…”

FRET efficiency and antenna effect in multi-color DNA origami-based light harvesting systems

“…21,22 Since every staple strand can be addressed and modied individually and separately, different moieties can be arranged with a high local control since the exact position of each staple strand in the DNA origami structure is known. DNA origami structures have been used to create highly sensitive SERS substrates by attaching gold nanoparticle dimers, [23][24][25] to analyze DNA strand breaks induced by low energy electrons 26,27 and UV photons 28 and to arrange different uo-rophores 29,29,30 at precise distances to create nanoscale photonic devices which can be used for example as photonic wires, 15,18 to resolve conformational changes of biomolecules, [31][32][33][34] as logic gates 35,36 and articial light harvesting complexes. 8,10,18 The light harvesting efficiency is in this context typically expressed as an antenna effect (AE), i.e.…”