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Base-specific Photocleavage of DNA Induced by Pazelliptine Sensitization: Study of the Mechanism by Time-resolved Absorption and Fluorescence
Marie-Pierre Fontaine-Aupart,
Eric Renault,
Christine Videlot,
Francis Tfibel,
Robert Pansu,
Michel Charlier,
Pascal Pernot,
Corresponding Author
Marie-Pierre Fontaine-Aupart
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
*Laboratoire de Photophysique Moléculaire, U.P.R. 3361 CNRS, Bâtiment 213, Université Paris-Sud, 91405 Orsay Cedex, France. Fax: 01 69 15 67 77; e-mail:[email protected]Search for more papers by this authorEric Renault
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorChristine Videlot
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorFrancis Tfibel
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorRobert Pansu
Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires, E.N.S Cachan, Cachan, France
Search for more papers by this authorMichel Charlier
Centre de Biophysique Moléculaire, Orléans, France
Search for more papers by this authorPascal Pernot
Laboratoire de Physico-Chimie des Rayonnements, Orsay, France
Search for more papers by this authorMarie-Pierre Fontaine-Aupart,
Eric Renault,
Christine Videlot,
Francis Tfibel,
Robert Pansu,
Michel Charlier,
Pascal Pernot,
Corresponding Author
Marie-Pierre Fontaine-Aupart
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
*Laboratoire de Photophysique Moléculaire, U.P.R. 3361 CNRS, Bâtiment 213, Université Paris-Sud, 91405 Orsay Cedex, France. Fax: 01 69 15 67 77; e-mail:[email protected]Search for more papers by this authorEric Renault
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorChristine Videlot
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorFrancis Tfibel
Laboratoire de Photophysique Moléculaire, UniversitéParis-Sud, Orsay, France
Search for more papers by this authorRobert Pansu
Laboratoire de Photophysique et Photochimie Supramoléculaires et Macromoléculaires, E.N.S Cachan, Cachan, France
Search for more papers by this authorMichel Charlier
Centre de Biophysique Moléculaire, Orléans, France
Search for more papers by this authorPascal Pernot
Laboratoire de Physico-Chimie des Rayonnements, Orsay, France
Search for more papers by this authorAbstract
The intercalating antitumoral drug pazelliptine (PZE) is able to photosensitize the formation of single- and double-strand breaks in supercoiled plasmid DNA and selective photocleavage at guanine residues is observed. In order to understand the mechanisms of DNA cleavage mediated by the photoexcited drug, singlet and triplet excited-state processes in PZE complexed with poly(dA-dT)-poly(dA-dT), poly(dG-dC)-poly(dG-dC) and calf thymus DNA have been investigated by means of single photon counting fluorescence decay and transient absorption techniques. For each complex, three different binding sites have been identified, due to the existence of different geometric structures of the drug in the ground state. For one type of binding site, a proton transfer reaction occurs in the singlet excited state whatever the nucleic acid environment. In contrast, the relaxation dynamics for the other two sites are found to depend widely upon the type of polynucleotide in which the drug has been intercalated. From the results of this study, we suggest that the photodynamic action of PZE does not originate from excitation of the drug in the environment of G-C base pairs but is initiated from its triplet state that reacts by electron transfer with the adenine bases. The specificity of cleavage could be the result of subsequent reactions leading to guanine oxidation.
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