title: Ultrafast Electron Transfer in Complexes of Doxorubicin with Human Telomeric G-Quadruplexes and GC Duplexes Probed by Femtosecond Fluorescence Spectroscopy.
abstract: Doxorubicin (DOX) is a natural anthracycline widely used in chemotherapy; its combined application as a chemotherapeutic and photodynamic agent has been recently proposed. In this context, understanding the photoinduced properties of DOX complexes with nucleic acids is crucial. Herein, the study of photoinduced electron transfer in DOX-DNA complexes by femtosecond fluorescence spectroscopy is reported. The behaviour of complexes with two model DNA structures, a G-quadruplex (G4) formed by the human telomeric sequence (Tel21) and a d(GC) duplex, is compared. The DOX affinity for these two sequences is similar. Although both 1:1 and 2:1 stoichiometries have been reported for DOX-G4 complexes, only 1:1 complexes form with the duplex. The steady-state absorption indicates a strong binding interaction with the duplex due to drug intercalation between the GC base pairs. In contrast, the interaction of DOX with Tel21 is much weaker and arises from drug binding on the G4 external faces at two independent binding sites. As observed for DOX-d(GC) complexes, fluorescence of the drug in the first binding site of Tel21 exhibits decays within a few picoseconds following a biphasic pattern; this is attributed to the existence of two drug conformations. The fluorescence of the drug in the second binding site of Tel21 shows slower decays within 150 ps. These timescales are consistent with electron transfer from the guanines to the excited drug, as favoured by the lower oxidation potential of the stacked guanines of G4 with respect to those in the duplex.
authors.affiliation: LIDYL, CEA, CNRS, Université Paris Saclay, F-91191, Gif-sur-Yvette, France. pascale.changenet-barret@polytechnique.edu.|LOB, CNRS, INSERM, Université Paris Saclay, 91128, Palaiseau, France. pascale.changenet-barret@polytechnique.edu.
authors.forename: Pascale
authors.identifier: 0000-0002-5874-6249
authors.initials: P
authors.lastname: Changenet-Barret
authors.affiliation: LIDYL, CEA, CNRS, Université Paris Saclay, F-91191, Gif-sur-Yvette, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustavsson
authors.affiliation: LIDYL, CEA, CNRS, Université Paris Saclay, F-91191, Gif-sur-Yvette, France.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Markovitsi
authors.affiliation: Istituto per la Sintesi Organica e la Fotoreattività, CNR, via P. Gobetti 101, 40129, Bologna, Italy. ilse.manet@isof.cnr.it.
authors.forename: Ilse
authors.initials: I
authors.lastname: Manet
mesh_terms: D004247:DNA / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry*; D004579:Electron Transport; D005454:Fluorescence Polarization; D054856:G-Quadruplexes; D006801:Humans; D013050:Spectrometry, Fluorescence / Q000379:methods*; D016615:Telomere
chemical_list: D004317:Doxorubicin; D004247:DNA
keywords: DNA; G-quadruplexes; antitumor agents; electron transfer; fluorescence