Chemistry Reference
In-Depth Information
5´- T
1
T
2
G
3
G
4
T
5
A
6
(T
1
T
2
+ G
3
TA) + (TTG
4
+ TA)
+ PCA
3´-A-A-C-C-A-T 3´-A-A-C-C-A-T
Scheme 1.1
Figure 1.3
Distribution of HOMOs (normalized to the largest value) in B-form duplex 5-mers
obtained by
ab initio
calculations. The arrows indicate the distribution of the HOMOs normal-
ized to the largest HOMO as 100
20
Further work by the Saito group involved
ab initio
calculations of HOMOs for
a wide variety of double - stranded G - containing 5 - mer sequences with B - form
geometry using GUSSIAN 9
x1
at the HF/6 - 31G * level.
19,20
For the quantum mechani-
cal studies, all of the sugar backbones of the 5-mers were removed from the coor-
dinate fi le and replaced by methyl groups. A few examples of the distributions of
HOMOs in the duplex 5-mers are shown in Figure 1.3.
The general trend for HOMO distribution is that the HOMO of stacked
GG doublets is localized overwhelmingly on the 5
-
fl anking residues (A, C or T). Bearing in mind that the model used is rather crude
(all of the sugar backbone replaced by methyl groups), further discussion of more
subtle sequence - specifi c differences is not warranted.
Further experimental support for the theoretical results was obtained by study-
ing the oxidation of oligodeoxynucleotides (ODN) with Co
2+
ions and benzoyl per-
oxide using PAGE analysis of the reaction mixture after hot piperidine treatment.
Sequence - dependent G - cleavage was observed for double - stranded ODN, whereas
nonselective equal G cleavage was observed for single-stranded ODN. The relative
rates of sequence oxidation were determined by densitometric assay of the ODN
cleavage bands. Experimentally observed relative rates of G oxidation matches well
with the calculated HOMOs of the G-containing sequences, implying that the Co
2+
ion is coordinated more strongly to the G having the larger HOMO.
20
Comparable theoretical calculations by Senthikumar
et al.
21
on stacked XGY
triplets with B-form geometries, including sugar and phosphate groups, show that
the site energy is strongly infl uenced by the type of nucleobase at the 3
′
-G, regardless of the 3
′
- and 5
′
′
position.
