Model studies on a carprofen derivative as dual photosensitizer for thymine dimerization and (6-4) photoproduct repair.

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.

• Authors: Jérôme Trzcionka, Virginie Lhiaubet-Vallet, Cecilia Paris, Noureddine Belmadoui, Maria José Climent, Miguel Angel Miranda
• Journal: Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 8 Issue 4 Pg. 402-7 (Mar 05 2007) ISSN: 1439-4227 [Print] Germany
• PMID: 17285658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbazoles
• Ethers, Cyclic
• Photosensitizing Agents
• carprofen
• oxetane
• Thymine

Topics

• Carbazoles (chemistry)
• Chromatography, High Pressure Liquid
• DNA Damage (radiation effects)
• DNA Repair (radiation effects)
• Dimerization
• Ethers, Cyclic (chemistry)
• Lasers
• Light
• Magnetic Resonance Spectroscopy
• Models, Biological
• Photolysis
• Photosensitizing Agents (chemistry)
• Spectrometry, Fluorescence
• Thymine (chemistry, radiation effects)