Chemistry Reference
In-Depth Information
upon the loss of a nucleobase. Hydrolytic depurination creates such a site (3.3 2-
dRs at pH 5.2 at 70 °C per h in pRSVneo plasmid DNA; Weinfeld et al. 1990), but it
is difficult to visualize such a site to be formed by free-radical reactions. Typically,
a fraction of the damaged base is still attached at the sugar moiety (for example, the
Fo lesion). On the nucleoside model level, 2-deoxyribose would have to be formed.
Thus far this has never been reported. Yet, subsequent hydrolytic treatment can
eliminate some of the damaged bases and create an 2-dR AP (see below).
For 2-dRL, the
C
(4
′
)-oxidized lesions (C4
′
-AP) and the lesion that has lost
C
(1
′
) (Erythrose-AP) is strong experimental evidence.
2dR and 2-dRL are in equilibrium with their ring-open forms, and thus all these
lesions can carry an OH group in
β
-position to a phosphate group. Like RNA
(OH group at
C
(2
)], such structures are alkali labile and release the phosphate
group upon treatment with alkali (Brown and Todd 1952; Chap. 13.2). For ex-
ample, this procedure was used for the detection of 2-dRL in
′
-irradiated DNA
(Dizdaroglu et al. 1977). At the time, it was not yet known that 2-dRL also gives
rise to 5-MF under such conditions (see below), and the reported yield (
G
= 0.01
×
γ
10
−7
mol J
−1
in N
2
O/O
2
-saturated solutions and
G
= 0.005
10
−7
mol J
−1
in N
2
O-
×
saturated solutions) must be on the low side.
The precursor of the 2-dRL lesion is the
C
(1
). The carbocation formed upon
its oxidation [reaction (2)] could react with water giving rise to a labile hemi-
aminal [reaction (3)] that would readily hydrolyze giving rise to the 2-dRL lesion
and an unaltered base [reaction (5)].
′
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