Guanine radicals duplexes

Our studies showed that i) substitution of an exocyclic amino group of dG is effective in modulating the chemical properties of dG toward one-electron oxidation, and ii) decomposition of the guanine radical cation was effectively suppressed near dphG. These results indicate that dphG is a prototype of nucleosides functioning as an intrinsic antioxidant of duplex DNA toward one-electron oxidation. 

Fig. 13 Results from the quantum calculations on the duplex sequence 5 -GAGG-3. In a, the sodium ions and their solvating water molecules are located at positions near the phosphate anions of the DNA backbone. In b, one sodium ion is moved from near a phosphate anion to N-7 of a guanine, which molecular dynamics calculations show to be a preferred site. The balloons represent the hole density on the GAGG sequences with the two different sodium ion orientations. The radical cation clearly changes its average location with movement of the sodium ion...

Figure 1 Free radical structures, parent compounds, and stable end products for the various components of DNA (a) deoxyribose, (b) guanine, (c) adenine, (d) thymine, and (e) cytosine. Panel (f) shows trapping of the electron and hole by proton transfer in the GC base pair in duplex DNA.

The effects of distance on the oxidation of guanine by 2AP radicals were studied using complementary duplexes (with T opposite 2AP) with the following 15-mer oligonucleotides, each containing a single 2AP base at the 5 -end [11, 13]. 

The spectra of the [2AP]Ti4 duplexes containing no guanines (Fig. 3a) are characterized by a bleaching of the 2AP absorption band near 310 nm, and the appearance of the absorption bands of the 2AP(-H) neutral radicals in DNA, the absorption maxima of these bands are observed at 365 nm (strong) and 510 nm (weak) [11]. The spectra obtained with the [2AP]GGTi2 duplexes containing no intervening bases between the electron donor and acceptor residues (Fig. 3b) exhibit the characteristic narrow absorption band near 310 nm typical of the G or G(-H) species with similar absorption spectra [48]. In our work, the formation of the G /G(-H) species oc-... 

The transient absorption spectra of duplexes with [2AP]A4GGAs are depicted in Fig. 5. At a delay time of 100 ns, the transient absorption spectrum is attributed to the superposition of the spectra of the 2AP(-H) and G /G (-H) radical products and the hydrated electrons. The structureless tail of the eh absorption in the 350-600 nm region decays completely within At<500 ns. The formation of G VG(-H) radicals monitored by the rise of the 310-nm absorption band and associated with the decay of the 2AP V 2AP(-H) transient absorption bands at 365 and 510 nm (Fig. 5) occurs in at least three well-separated time domains (Fig. 6). The prompt (<100 ns) rise of the transient absorption at 312 nm due to guanine oxidation by 2AP was not resolved in our experiments. However, the ampHtude, A((=ioo), related to the prompt formation of the G /G(-H) radicals (Fig. 6a) can be estimated using the extinction coefficients of the radical species at 312 and 330 nm (isosbestic point) [11]. The kinetics of the G VG(-H) formation in the yits and ms time intervals were time-resolved and characterized by two well-defined components shown in Fig. 6a (0.5 /zs) and Fig. 6b (60 /zs). 

Table 2 Deuterium isotope effect on the rate constants of the oxidation of guanine and 8-oxoguanine by 2-aminopurine neutral radicals in double-stranded DNA duplexes (adapted from [11] and [13]) ...

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