title: A synthetic oligonucleotide model for evaluating the oxidation and crosslinking propensities of natural furan-modified DNA.
abstract: We have previously developed a crosslinking methodology for oligonucleotides based on the incorporation of furan moieties, which can be selectively oxidised to reactive intermediates that will quickly react with the opposite bases in DNA, forming toxic interstrand crosslinks (ICLs). Furan moieties also occur in natural DNA, as a result of oxidative stress. Moreover, the furan-containing degradation product of this modified DNA-kinetin-has been found to display beneficial anti-ageing effects. To investigate the apparent discrepancy between the effects of the synthetic and the natural furan modifications in DNA, a quick and easy postsynthetic method providing access to the natural modification in short synthetic oligonucleotides was developed. On checking for potential crosslinking propensity, we found that the furan moiety does indeed undergo oxidation, in this way functioning as an important scavenger for oxidative stress. The reactive intermediate, however, was shown to degrade without producing toxic crosslinked products.
authors: Organic and Biomimetic Chemistry Research Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4, 9000 Gent (Belgium). lieselot.carrette@ugent.be.
authors: Lieselot L G
authors: LL
authors: Carrette
authors: Annemieke
authors: A
authors: Madder
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000737:chemistry / Q000378:metabolism; D005663:Furans / Q000737:chemistry*; D007701:Kinetin / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D003432:Cross-Linking Reagents; D016166:Free Radical Scavengers; D005663:Furans; D009841:Oligonucleotides; D004247:DNA; D007701:Kinetin; C039281:furan
keywords: DNA damage; antioxidants; biomimetic synthesis; kinetin; oligonucleotides