Independent generation and reactivity of 2-deoxy-5-methyleneuridin-5-yl, a significant reactive intermediate produced from thymidine as a result of oxidative stress.
2'-Deoxy-5-methyleneuridin-5-yl (1) is produced in a variety of DNA damage processes and is believed to result in the formation of lesions that are mutagenic and refractory to enzymatic repair. 2'-Deoxy-5-methyleneuridin-5-yl (1) was independently generated under anaerobic conditions via Norrish Type I photocleavage during Pyrex filtered photolysis of the benzyl ketone 7. The radical (1) exhibits behavior consistent with that of a resonance-stabilized radical. The KIE for hydrogen atom transfer from t-BuSH was found to be 7.3 +/- 1.7. Competition studies between radical recombination and hydrogen atom donors (2,5-dimethyltetrahydrofuran, kTrap = 46.1 +/- 15.4 M(-1) s(-1); propan-2-ol, kTrap = 13.6 +/- 3.5 M(-1) s(-1)) chosen to mimic the carbohydrate components of 2'-deoxyribonucleotides suggest that 2'-deoxy-5-methyleneuridin-5-yl (1) may be able to transfer damage from the nucleobase to the deoxyribose of an adjacent nucleotide in DNA under hypoxic conditions.
Anderson
A S
AS
Department of Chemistry, Colorado State University Fort Collins, 80523, USA.
Hwang
J T
JT
Greenberg
M M
MM
D004249:DNA Damage / Q000528:radiation effects; D003854:Deoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D003855:Deoxyribose / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D005609:Free Radicals / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects; D005663:Furans / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008623:Mercaptoethanol / Q000378:metabolism; D018384:Oxidative Stress / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D010782:Photolysis / Q000528:radiation effects; D013936:Thymidine / Q000737:chemistry* / Q000378:metabolism / Q000528:radiation effects*; D014529:Uridine / Q000737:chemistry* / Q000378:metabolism* / Q000528:radiation effects
C415331:2'-deoxy-5-methyleneuridin-5-yl; D003854:Deoxyribonucleotides; D005609:Free Radicals; D005663:Furans; C051333:2,5-dimethyltetrahydrofuran; D003855:Deoxyribose; D008623:Mercaptoethanol; D006859:Hydrogen; D010100:Oxygen; D013936:Thymidine; D014529:Uridine