Model Studies on a Carprofen Derivative as Dual Photosensitizer for Thymine Dimerization and (6–4) Photoproduct Repair
✍ Scribed by Jérôme Trzcionka; Virginie Lhiaubet-Vallet; Cecilia Paris; Noureddine Belmadoui; Maria José Climent; Miguel Angel Miranda
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 122 KB
- Volume
- 8
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Abstract
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.