62962-42-9Relevant articles and documents
Tri-cyclic nucleobase analogs and their ribosides as substrates of purine-nucleoside phosphorylases. II guanine and isoguanine derivatives
Stachelska-Wierzchowska, Alicja,Wierzchowski, Jacek,Górka, Micha?,Bzowska, Agnieszka,Wielgus-Kutrowska, Beata
, (2019)
Etheno-derivatives of guanine, O6-methylguanine, and isoguanine were prepared and purified using standard methods. The title compounds were examined as potential substrates of purine-nucleoside phosphorylases from various sources in the reverse (synthetic) pathway. It was found that 1,N2-etheno-guanine and 1,N6-etheno-isoguanine are excellent substrates for purine-nucleoside phosphorylase (PNP) from E. coli, while O6-methyl-N2,3-etheno-guanine exhibited moderate activity vs. this enzyme. The latter two compounds displayed intense fluorescence in neutral aqueous medium, and so did the corresponding ribosylation products. By contrast, PNP from calf spleens exhibited only modest activity towards 1,N6-etheno-isoguanine; the remaining compounds were not ribosylated by this enzyme. The enzymatic ribosylation of 1,N6etheno-isoguanine using two forms of calf PNP (wild type and N243D) and E. coli PNP (wild type and D204N) gave three different products, which were identified on the basis of NMR analysis and comparison with the product of the isoguanosine reaction with chloroacetic aldehyde, which gave an essentially single compound, identified unequivocally as N9-riboside. With the wild-type E. coli enzyme as a catalyst, N9-β-d- and N7-β-d-ribosides are obtained in proportion ~1:3, while calf PNP produced another riboside, tentatively identified as N6-β-d-riboside. The potential application of various forms of PNP for synthesis of the tri-cyclic nucleoside analogs is discussed.
4-Hydroxy-2-nonenal and ethyl linoleate form N2,3-ethenoguanine under peroxidizing conditions
Ham, Amy-Joan L.,Ranasinghe, Asoka,Koc, Hasan,Swenberg, James A.
, p. 1243 - 1250 (2007/10/03)
In these studies, we demonstrate that N2,3-ethenoguanine (N2,3-∈Gua) is formed from lipid peroxidation as well as other oxidative reactions. Ethyl linoleate (EtLA) or 4-hydroxy-2-nonenal (HNE) was reacted with dGuo in the presence of tert-butyl hydroperoxide (t-BuOOH) for 72 h at 50 °C. The resulting N2,3-∈Gua was characterized by liquid chromatography/electrospray mass spectroscopy and by gas chromatography/high-resolution mass spectral (GC/HRMS) analysis of its pentafluorobenzyl derivative following immunoaffinity chromatography purification. The amounts of N2,3-∈Gua formed were 825 ± 20 and 1720 ± 50 N2,3-∈Gua adducts/106 normal dGuo bases for EtLA and HNE, respectively, corresponding to 38- and 82-fold increases in the amount of N2,3-∈Gua compared to controls containing only t-BuOOH. Controls containing t-BuOOH but no lipid resulted in a > 1000-fold increase in the level of N2,3-∈Gua over dGuo that was not subjected to incubation. EtLA and HNE, in the presence of t-BuOOH, were reacted with calf thymus DNA at 37 °C for 89 h. The amounts of N2,3-∈Gua formed in intact ctDNA were 114 ± 32 and 52.9 ± 16.7 N2,3-∈Gua adducts/106 normal dGuo bases for EtLA and HNE, respectively. These compared to 2.02 ± 0.17 and 2.05 ± 0.47 N2,3-∈Gua adducts/106 normal dGuo bases in control DNA incubated with t-BuOOH, but no lipid [13C18]EtLA was reacted with dGuo to determine the extent of direct alkylation by lipid peroxidation byproducts. These reactions resulted in a 89-93% level of incorporation of the 13C label into N2,3-∈Gua when EtLA and dGuo were in equimolar concentrations, when EtLA was in 10-fold molar excess, and when deoxyribose (thymidine) was in 10-fold molar excess. Similar reactions with ctDNA resulted in an 86% level of incorporation of the 13C label. These data demonstrate that N2,3-∈Gua is formed from EtLA and HNE under peroxidizing conditions by direct alkylation. The data also suggest, however, that N2,3-∈Gua is also formed by an alternative mechanism that involves some other oxidative reaction which remains unclear.
Synthesis and Properties of N2,3-Ethenoguanosine and N2,3-Ethenoguanosine 5'-Diphosphate
Kusmierek, Jaroslaw T.,Jensen, David E.,Spengler, Sylvia J.,Stolarski, Ryszard,Singer, B.
, p. 2374 - 2378 (2007/10/02)
N2,3-Ethenoguanosine has not been reported as a product of guanosine reaction with haloacetaldehydes.This is in contrast to the reaction of the ribosides yielding the well-known etheno compounds 1,N6-εAdo, 3,N4-εCyd, and 1,N2-εGuo.The base, N2,3-ethenoguanine was, however, synthesized, but not by direct reaction.We now report the synthesis of the nucleoside via reaction of O6-benzylguanosine with bromoacetaldehyde followed by hydrogenolytic debenzylation in the presence of palladium on charcoal.The structure of N2,3-ethenoguanosine was confirmed by NMR, UV, and FAB-MS data.The conformation of this nucleoside resembles that of guanosine, being predominantly in the anti form.The nucleoside was stable at neutrality, 37 deg C, but depurination was rapid at pH 1,24 deg C, with a t1/2 = 16 min.In contrast to 1,N2-εGuo, the angular N2,3-etheno derivatives are fluorescent, with the base having considerably higher fluorescence than the nucleoside.N2,3-Ethenoguanosine was converted to the 5'-diphosphate by conventional methods.This compound was a substrate for polynucleotide phosphorylase and could be copolymerized with CDP or ADP.There is little quench of the nucleotide fluorescence in copolymers.The recent report that N2,3-ethenoguanine is detected in chloroacetaldehyde-treated DNA after depurination makes N2,3-etheno modification of the guanine moiety of potential importance in understanding vinyl chloride induced carcinogenesis.
