title: Photooxidation of d(TpG) by phthalocyanines and riboflavin. Isolation and characterization of dinucleoside monophosphates containing the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxy-guanosine.
abstract: Phthalocyanine mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen saturated aqueous solution has previously been shown to result in the addition of molecular oxygen to the guanine base generating the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine (dO) (the asterisk denotes unambiguous assignment of the 4R and 4S diastereoisomers). The data presented here show that the same guanine modified bases are generated in a 1:1 ratio when thymidylyl-(3',5')-2'-deoxyguanosine (d(TpG)) is similarly photo-oxidized. These modified dinucleoside monophosphates, labelled d(TpO)-A and -B, have been isolated by high performance liquid chromatography and characterized by proton NMR spectrometry, fast atom bombardment mass spectrometry, and enzymatic digestions. Photosensitization in D2O instead of H2O leads to an increase in the rate of d(TpO) formation that is consistent with a type II (singlet oxygen) reaction mechanism. Three interesting properties of these modified dinucleoside monophosphates are: i) the rate of their digestion with spleen phosphodiesterase is greatly reduced relative to d(TpG), ii) they are not digested by snake venom phosphodiesterase, and iii) they are stable to 1.0 M piperidine at 90 degrees C for 30 min. The latter observation indicates that 4,8-dihydro-4-hydroxy-8-oxoguanine is not a base lesion responsible for the strand breaks observed following hot piperidine treatment of DNA exposed to type II photosensitizers or chemically generated singlet oxygen.
authors.affiliation: Laboratoire des Lésions des Acides Nucléiques, DRFMC/SESAM, Centre d'Etudes Nucléaires de Grenoble, France.
authors.forename: G W
authors.initials: GW
authors.lastname: Buchko
authors.forename: J
authors.initials: J
authors.lastname: Cadet
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: J L
authors.initials: JL
authors.lastname: Ravanat
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D015226:Dinucleoside Phosphates / Q000737:chemistry* / Q000302:isolation & purification*; D007211:Indoles; D054833:Isoindoles; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010727:Phosphoric Diester Hydrolases; D010777:Photochemistry; D011838:Radiation-Sensitizing Agents; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D015226:Dinucleoside Phosphates; D007211:Indoles; D054833:Isoindoles; D011838:Radiation-Sensitizing Agents; C077119:4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine; C077117:thymidylyl-(3',5')-2'-deoxyguanosine; D004247:DNA; D010727:Phosphoric Diester Hydrolases; D003849:Deoxyguanosine; D013941:Thymine; C013647:phthalocyanine