Photochemical Generation of a C5'-Uridinyl Radical.
It has been postulated that sugar radicals and related species are involved in oxidative events involving RNA. To determine the contribution, if any, of these species to the deleterious effects of the endogenous exposome, it is important to unambiguously identify their degradation products. C5'-Pivaloyl uridine was successfully synthesized and subsequently photolytically converted to a C5'-uridinyl radical. Generation of the radical under anaerobic conditions in the presence of glutathione led to the formation of the expected reduction product, uridine. However, regardless of the presence or absence of reductant, the base elimination product, uracil, was also observed. Mass balances and product distributions were dependent upon the pH of the photolysis mixture. At low pH, trapping with glutathione successfully competed with base loss. These results indicate that this precursor should function efficiently in an investigation of the fate of the C5'-uridinyl radical in RNA oligomers.
Unicon Pharma, Inc., 2015 Lincoln Highway Suite 234, Edison, NJ, 08817, USA.
Raziya
R
Shaik
Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 W Bancroft Street, MS 606, Toledo, OH, 43606, USA.
Matthew W
MW
Ellis
Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 W Bancroft Street, MS 606, Toledo, OH, 43606, USA.
Matthew J
MJ
Starr
Department of Chemistry, The University of California, Riverside, 501 Big Springs Road, Riverside, CA, 92521, USA.
Nicholas J
NJ
Amato
Department of Medicinal and Biological Chemistry, The University of Toledo, 2801 W Bancroft Street, MS 606, Toledo, OH, 43606, USA. abryant9@utnet.utoledo.edu.
Amanda C
AC
Bryant-Friedrich
D018360:Crystallography, X-Ray; D005609:Free Radicals / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008027:Light; D008968:Molecular Conformation; D010782:Photolysis / Q000528:radiation effects; D012313:RNA / Q000737:chemistry; D014529:Uridine / Q000138:chemical synthesis / Q000737:chemistry*
D005609:Free Radicals; D012313:RNA; D005978:Glutathione; D014529:Uridine
exposome; nucleosides; organic chemistry; oxidative damage; photolysis