Chemistry Reference
In-Depth Information
deoxytrinucleotide cis-[Pt(NH
3
)
2
(d(CpGpG))] is shown in
Figure 22.7
.
Figure 22.8
presents the X-ray structure at
2.6-
˚
resolution of a double-stranded DNA dodecamer containing this adduct.
FIGURE 22.7
X-Ray structure of d(CGG) chelated to a cisplatin unit.
(From
Reedijk, 2003
. Copyright 2003 with permission from US
National Academy of Sciences.)
FIGURE 22.8
X-Ray structure showing the kinking of DNA by cisplatin (PDB1AIO).
It seems to be generally accepted that the anti-tumour activity of cisplatin is mediated by the recognition of the
platinated adducts by cellular proteins. In particular, HMG (high-mobility group) proteins, which are believed to
play a key role in the regulation of gene expression (transcription), have been found to specifically recognise and
bind to cisplatin-modified DNA (
Figure 22.6
). It has been suggested that HMG proteins play a role in the
