Guanine methylated

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

Cleavage at A or G If the DNA is first treated with acid, dimethyl sulfate methylates adenine at the 3-position as well as guanine at the 7-position (not shown). Subsequent reaction with OH and piperidine triggers degradation and displacement of the methylated A or G purine base and strand scission, essentially as indicated here for reaction of dimethyl sulfate with guanine. 

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, Kramer T, Niewohner U, Pleiss U, Stoltefuss J et al. (2003) Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science 299 893-896 Ehon GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, Schaeffer HJ (1977) Selectivity of action of an antiherpetic agent, 9-(2-hydroxy ethoxy methyl) guanine, Proc Natl Acad Sci USA 74 5716-5720... 

Small quantities of additional purines and pyrimidines occur in DNA and RNAs. Examples include 5-methyl-cytosine of bacterial and human DNA, 5-hydroxy-methylcytosine of bacterial and viral nucleic acids, and mono- and di-N-methylated adenine and guanine of... 

The reactions of the oxadiazolium ions with nucleophiles such as thiophenolSy guanine, and guanosine resulted in methylation of the nucleophiles (53). Thus, the formation of the oxadiazolium ion creates an electrophilic species not... 

Nucleobases, including 9-methyl-, 9-ethyl-, 1,9-dimethyl-guanine and 2-amino-6-methoxy-9-methylpurine, form complexes of the type Au(N)Cl3 when reacted with [AuCU] in water at pH 3—4. Binding of a AuCh unit to the N (7) position of the purine ring was confirmed by X-ray crystallography [26]. 

There are examples in which base radicals undergo reaction with adjacent base residues. The 5-(2 -deoxyuridinyl)methyl radical (63, Scheme 8.30) can forge an intrastrand cross-link with adjacent purine residues. Cross-link formation is favored with a guanine residue on the 5 -side of the pyrimidine radical and occurs under low-oxygen conditions. A mechanism was not proposed for this process, but presumably the reaction involves addition of the nucleobase alkyl radical to the C8-position of the adjacent purine residue. Molecular oxygen likely inhibits crosslink formation by trapping the radical 63, as shown in Scheme 8.24. The radical intermediate 89 must undergo oxidation to yield the final cross-linked product 90,... 

The effect of the aqueous medium on the reactivity and on the stability of the resulting adducts has been investigated to assess which adduct arises from the kinetically favorable path or from an equilibrating process. The calculations indicate that the most nucleophilic site of the methyl-substituted nucleobases in the gas phase is the guanine oxygen atom, followed by the adenine N1, while other centers exhibit a substantially lower nucleophilicity (see activation Gibbs energies in Table 2.2). 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

Zgierski and coworkers proposed for guanine the same biradical mechanism that was proposed for all the other bases [172], Furthermore, on the fly molecular dynamics using density functional theory have been used to study initial evolution along the Si surface of methylated guanine [167-169],... 

Langer H, Doltsinis NL (2003) Selected photostabilisation of guanine by methylation. Phys Chem Chem Phys 5 4516-4518... 

Experiments with methyl guanine (27), in which the acidic proton of the radical cation is exchanged by a methyl group, support this explanation [22]. With this base in a mismatch situation (strand 25) the hole transfer becomes efficient again because a deprotonation cannot occur (Fig. 15). 

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