Model studies on a carprofen derivative as dual photosensitizer for thymine dimerization and (6-4) photoproduct repair.
Cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts are among the main UV-induced DNA lesions. Both types of damage are mostly repaired in prokaryotes by photolyase enzymes. The repair mechanism of (6-4) photolyases has still not been fully elucidated, but it is assumed that back rearrangement to the oxetane occurs prior to repair. In this work, a non-steroidal anti-inflammatory drug derivative corresponding to the dechlorinated methyl ester of carprofen (namely methyl 2-(carbazol-2-yl)propanoate, PPMe) has been used to achieve the photosensitized cycloreversion of model oxetanes (formally resulting from photocycloaddition between benzophenone and 1,3-dimethylthymine or 2'-deoxyuridine), by employing fluorescence spectroscopy, laser flash photolysis, HPLC and NMR. Although PPMe is able to photoinduce the cycloreversion of both oxetanes, the fluorescence quenching of PPMe is faster for the 2'-deoxyribose-containing oxetane; this underlines the importance of the structure in such studies. Moreover, PPMe was shown to photoinduce the formation of thymidine cyclobutane dimers through a triplet-triplet energy transfer from a vibrationally excited state, as suggested by the enhanced PPMe triplet quenching by thymidine with increasing temperature. These results reveal a dual role of PPMe in DNA photosensitization, in that it photoinduces either damage or repair.
Trzcionka
Jérôme
J
Instituto de Tecnología Química UPV-CSIC, Departamento de Química, Universidad Politécnica de Valencia, Avenida de los Naranjos s/n, 46022 Valencia, Spain.
Lhiaubet-Vallet
Virginie
V
Paris
Cecilia
C
Belmadoui
Noureddine
N
Climent
Maria José
MJ
Miranda
Miguel Angel
MA
D002227:Carbazoles / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D019281:Dimerization; D004988:Ethers, Cyclic / Q000737:chemistry*; D007834:Lasers; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013941:Thymine / Q000737:chemistry* / Q000528:radiation effects
D002227:Carbazoles; D004988:Ethers, Cyclic; D017319:Photosensitizing Agents; C007005:carprofen; C005287:oxetane; D013941:Thymine