Chemistry Reference
In-Depth Information
5.1.2 DNA Binding
Because platinum belongs to the group of 'soft' metal ions, it reacts preferentially
with N atoms rather than O atoms. In fact, the preferred binding site in DNA is N7
of purine nucleobases.
39 - 45
It has been suggested that
in vivo
the positively charged
cis
- [Pt(NH
3
)
2
(OH
2
)
2
]
2+
ion diffuses to the negatively charged DNA and then rapidly
migrates along the helix to the preferred d(GpG) binding sites.
46
A scheme with all
potential binding sites is represented in Figure 5.2.
In double-stranded DNA the only nitrogen atoms which are not involved in
Watson-Crick hydrogen bonds and are available for coordination to Pt are N3 and
N7 of purines. However N3 is sterically hindered, therefore only N7 is left (bold
arrows in Figure 5.2). In single-stranded DNA N1 of adenine and N3 of cytosine
are also capable of Pt binding (dotted arrows in Figure 5.2). Finally, all protonated
nitrogen atoms of purines and pyrimidines have the lone pair of electrons delocal-
ized on the aromatic p-system of the ring they belong or are attached to, therefore
they become available for coordination to Pt only after deprotonation (empty
arrows in Figure 5.2 ).
NH
2
cytosine (C)
4
N
5
3
6
2
1
N
O
HO
O
O
H
H
guanine (G)
N
7
6
NH
H
H
1
2
5
O
H
8
4
N
9
3
O
P
O
NH
2
N
NH
2
O
H
H
O
-
N
7
6
N
H
H
5
1
2
O
H
adenine (A)
8
4
9
3
N
O
P
O
N
O
O
H
H
O
-
4
NH
3
5
6
H
H
O
H
= preferential platination sites
in double-strand DNA
2
1
O
P
O
O
O
= additional metal binding sites
in single-strand DNA
thymine (T)
H
H
O
-
= potential metal binding sites
only after loss of a proton
H
H
OH
H
Figure 5.2
Possible platinum binding sites on DNA
