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1 June 2003 Photosensitization of DNA Damage by a New Cationic Pyropheophorbide Derivative: Sequence-specific Formation of a Frank Scission
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Pyropheophorbides are red-absorbing porphyrin-like photosensitizers that may interact with DNA either by intercalation or by external binding with self-stacking according to the value of the nucleotide to chromophore molar ratio (N/C). This article reports on the nature and sequence selectivity of the DNA damage photoinduced by a water-soluble chlorhydrate of aminopyropheophorbide. First, this pyropheophorbide is shown to induce on irradiation the cleavage of ΦX174 DNA by both Type-I and -II mechanisms, suggested by scavengers and D2O effects. These conclusions are then improved by sequencing experiments performed on a 20-mer oligodeoxynucleotide (ODN) irradiated at wavelengths >345 nm in the presence of the dye, N/C varying from 2.5 to 0.5. Oxidation of all guanine residues to the same extent is observed after piperidine treatment on both single- and double-stranded ODN. Moreover, unexpectedly, a remarkable sequence-selective cleavage occurring at a 5′-CG-3′ site is detected before alkali treatment. This frank break is clearly predominant for a low nucleotide to chromophore molar ratio, corresponding to a self-stacking of the dye along the DNA helix. The electrophoretic properties of the band suggest that this lesion results from a sugar oxidation, which leads via a base release to a ribonolactone residue. The proposal is supported by high-performance liquid chromatography–matrix-assisted laser desorption-ionization mass spectrometry experiments that also reveal other sequence-selective frank scissions of lower intensity at 5′-GC-3′ or other 5′-CG-3′ sites. This sequence selectivity is discussed with regard to the binding selectivity of cationic porphyrins.

Claire Kanony, Anne-Sylvie Fabiano-Tixier, Jean-Luc Ravanat, Patricia Vicendo, and Nicole Paillous "Photosensitization of DNA Damage by a New Cationic Pyropheophorbide Derivative: Sequence-specific Formation of a Frank Scission," Photochemistry and Photobiology 77(6), 659-667, (1 June 2003).<0659:PODDBA>2.0.CO;2
Received: 11 February 2003; Accepted: 1 March 2003; Published: 1 June 2003

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