Benzophenone photosensitization of 2'-deoxyguanosine: characterization of the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)- 2-methoxy-4,5-imidazolidinedione. A model system for the investigation of photosensitized formation of DNA-protein crosslinks.
Benzophenone-mediated photosensitization of 2'-deoxyguanosine and its 3',5'-di-O-acetyl derivative, used as DNA model compounds, in oxygen-saturated water-methanol (1:1) solution results in the nucleophilic addition of methanol to the guanine base. The resulting modified nucleosides have been isolated by reverse-phase high-performance liquid chromatography and characterized by extensive spectroscopic measurements including 13C and 1H nuclear magnetic resonance, fast atom bombardment mass spectrometry and circular dichroism as the 2R and 2S diastereoisomers of 1-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-methoxy-4,5-imidazolinedione and their related 3',5'-di-O-acetyl derivates. Information concerning the absolute configuration of the two pairs of diastereoisomers was inferred from detailed nuclear Overhauser effect experiments. A reaction mechanism, involving guanine radical intermediates, is proposed to explain the generation of these new guanine photoproducts.
Morin
B
B
CEA/Département de Recherche Fondamentale sur la Matière Condensée, SESAM/LAN, Grenoble, France.
Cadet
J
J
D001577:Benzophenones / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D004247:DNA / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000737:chemistry / Q000528:radiation effects*; D003853:Deoxyribonucleosides / Q000528:radiation effects*; D007093:Imidazoles / Q000528:radiation effects*; D048289:Imidazolidines; D008956:Models, Chemical; D010777:Photochemistry; D011506:Proteins / Q000528:radiation effects; D013237:Stereoisomerism
C089923:1-(2-deoxypentofuranosyl)-2-methoxy-4,5-imidazolidinedione; D001577:Benzophenones; D003432:Cross-Linking Reagents; D003853:Deoxyribonucleosides; D007093:Imidazoles; D048289:Imidazolidines; D011506:Proteins; C047723:benzophenone; D004247:DNA; D003849:Deoxyguanosine