Chemistry Reference
In-Depth Information
When C or T is present at the 3
position, the site energy at the guanine was found
to be up to 0.44 eV higher than for A or G at this position. The infl uence of the base
at the 5
′
position was much smaller, the variation in site energy being less than
0.1 eV. The amount of charge on a certain G was calculated from the coeffi cients of
the guanine fragment orbitals. It was concluded that the neighbouring base at the
3
′
position to a large extent determines the charge distribution and therefore the
oxidative damage on a sequence of guanine bases.
21
Further work by the Saito group on experimental mapping of G-rich hot spots
included photo-induced cleavage of double-stranded
32
P - end - labelled oligodeoxy-
nucleotides (ODNs) 30-mers possessing two different G-containing sequences (5
′
′
-
step as a standard on the same strand.
22
Under low
photo-irradiation conditions, only the cleavage bands of 5
T XGY T - 3
′
) and a 5
′
- T TGG T - 3
′
-Gs of the two GG steps
and the middle step of the GGG triplet were observed by hot piperidine treatment.
Quantitative densitometric assay was used to determine the relative amounts of
cleavage products. The experimental results were compared to IP values calculated
for 16 sets of base-paired G- and GG-containing 5-mers. A plot of the log of the
relative reactivity (
k
rel
) toward photo - induced one - electron oxidation versus calcu-
lated IP is shown in Figure 1.4.
A different explanation for the enhanced reactivity of the 5
′
′
-G of a GG step
-G is presented by the Schuster group.
23
Theoretical calculations
of base - paired quartets, d(5
compared to the 3
′
), suggested that electronic
factors may not be the primary determinant of the reaction selectivity for GG steps.
Instead the authors propose, based on molecular dynamic (MD) simulations on B-
DNA oligomers, d(5
′
- XGGX - 3
′
)/d(5
′
- YCCY - 3
′
), where X = A,T,U
and Y is the complementary base, that 'there is an important steric contribution to
the preference for reaction at the 5
′
- GXXGGXXG - 3
′
)/d(5
′
- GYYGGYYG - 3
′
- G in the GG doublets ' . Photo - cleavage experi-
ments carried out on the series of B-DNA oligomers showed that for GG steps in
′
Figure 1.4
A plot of the log of the relative reactivity (
k
rel
) toward photo-induced one-electron
oxidation versus calculated ionization potential (IP). The relative reactivity was obtained from
densitometric assay of G bands with TGG as a standard (
k
rel
= 1.0) under single-hit conditions.
(Reprinted with permission from
J. Am. Chem. Soc.
, 1998,
120
, 12687. Copyright 1998
American Chemical Society.)
