title: Isomerization of 5-Hydroxy-5-methylhydantoin 2'-Deoxynucleoside into α-Furanose, β-Furanose, α-Pyranose, and β-Pyranose Anomers.
abstract: Oxidative damage is one of the most frequent types of DNA damage resulting from biologically generated oxygen or nitrogen reactive species. Hydroxyl radicals, one electron oxidants, and various chemical oxidants, such as permanganate and ozone, react with pyrimidine bases in DNA, cytosine and thymine, to produce 5-hydroxyhydantoin derivatives. 5-Hydroxyhydantoin modifications are interesting because they undergo ring-chain tautomerism into a pair of diastereomers via an open chain carbonyl intermediate. Here, we show that purified diastereomers of N1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin not only undergo isomerization into a mixture of 5R and 5S diastereomers of the hydantoin ring but also into three additional pairs of diastereomers, in which the sugar moiety transforms into α-furanose, β-pyranose, and α-pyranose anomers. The novel 5-hydroxy-5-methylhydantoin derivatives were characterized by extensive NMR analyses. Further studies indicate that isomerization is greatly suppressed at pH 6 compared to that at higher pH. A novel mechanism of isomerization is proposed to account for the formation of nucleoside anomers at neutral pH, which involves ring-chain tautomerism of both the hydantoin and sugar moieties. Last, the isomerization of β-furanose into the corresponding α-furanose is shown to take place in purified DNA, albeit to a slower extent than that in solution. The ability of 5-hydroxyhydantoin nucleosides to undergo isomerization may complicate the biological processing of this damage in cellular DNA.
authors.affiliation: Département de Médecine Nucléaire et de Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke , 3001, 12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Anum
authors.initials: A
authors.lastname: Ali
authors.affiliation: Département de Médecine Nucléaire et de Radiobiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke , 3001, 12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004249:DNA Damage; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology; D006827:Hydantoins / Q000737:chemistry / Q000494:pharmacology*; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: C000612302:5-hydroxy-5-methylhydantoin 2'-deoxynucleoside; D005663:Furans; D006827:Hydantoins; D009705:Nucleosides; D011714:Pyrans; D004247:DNA; C427203:calf thymus DNA