Chemistry Reference
In-Depth Information
N7 of both adenine and guanine can be platinated, however N7 of guanine
shows a greater kinetic preference.
35,42
This tendency results from the stronger basic-
ity of that nitrogen and from possible simultaneous hydrogen-bond interactions
between am(m)ine protons of cisplatin and O6 of guanine.
34
In contrast, in the case
of adenine, only repulsive interactions can be produced between the NH
2
in position
6 of adenine and a platinum-bonded amine ligand.
47
The reaction of cisplatin with DNA leads to the formation of at least six dif-
ferent types of Pt-DNA adducts, the most important being schematically depicted
in Figure 5.3. The major adduct formed by cisplatin was found to be the 1,2-
intrastrand crosslink between adjacent guanine bases (d(GpG), 60-65%), followed
by the 1,2-intrastrand crosslink between adjacent adenine and guanine bases
(d(ApG), 20-25%); 1,3 and 1,4-intrastrand crosslinks between purines separated by
one (d(GXG), X stands for a deoxyribonucleotide, 5-6%) or two intervening bases
(d(GXXG)) can also occurr.
48 - 51
It can be noticed how intrastrand d(GpG) and
d(ApG) adducts together account for about 90% of the total. A small percentage
of cisplatin was found to be involved in interstrand crosslinks between two guanines
on opposite strands of the DNA, in monofunctional adducts in which the platinum
NH
3
(b)
Pt
NH
3
NH
3
Pt
(c)
NH
3
(d)
NH
3
NH
3
Pt
NH
3
Pt
NH
3
PROTEIN
(a)
Figure 5.3
Main adducts formed in the interaction of cisplatin with DNA: (a) 1,2-intrastrand
crosslink; (b) 1,3-intrastrand crosslink; (c) interstrand crosslink; (d) protein-DNA crosslink
