Type I benzophenone-mediated nucleophilic reaction of 5'-amino-2',5'-dideoxyguanosine. A model system for the investigation of photosensitized formation of DNA-protein cross-links.
5'-Amino-2',5'-dideoxyguanosine has been synthesized in order to investigate the intramolecular reactivity of an amino group toward the guanine radical produced by type I photosensitization mechanism. Benzophenone-mediated photosensitization of 5'-amino-2',5'-dideoxyguanosine in aerated aqueous solution results in the formation of a predominant cyclic nucleoside together with an unstable nucleoside precursor. The two modified nucleosides have been isolated by reverse phase high performance liquid chromatography and characterized by spectroscopic measurements including 13C and 1H NMR, fast atom bombardment mass spectroscopy, and UV absorption. The stable photoproduct has been identified as 9-oxa-2,4-diazabicyclo[4.2.1]non-2-en-7-ol, 3-amino- (1R-exo), whereas its precursor has been assigned as acetic acid, [(7-hydroxy-9-oxa-2,4-diazabicyclo[4.2.1]non-2-en-3-yl)amino]oxo- (1R-exo). A reaction mechanism, involving nucleophilic addition of the sugar amino group to guanine radical intermediates, is proposed to explain the formation of the two photoproducts.
Morin
B
B
CEA/Département de Recherche Fondamentale sur la Matière Condensée, SESAM/LAN, Grenoble, France.
Cadet
J
J
D001577:Benzophenones / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D015224:Dideoxynucleosides / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D017319:Photosensitizing Agents / Q000737:chemistry*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet
C096098:5'-amino-2',5'-dideoxyguanosine; D001577:Benzophenones; D003432:Cross-Linking Reagents; D015224:Dideoxynucleosides; D017319:Photosensitizing Agents; D011506:Proteins; C047723:benzophenone; D004247:DNA