DNA, platinated

Brown, S.J, Kellett, P.J., and Lippard, S.J. (1993) Ixrl, a yeast protein that binds to platinated DNA and confers sensitivity to cisplatin. Science 261, 603-605. 

Fig. 3 Structure of fullerenes Cso, C70, Cso and single-wall carbon nanotube. The figures were taken with permission of Prof. C. Dekker from the image gallery found at http //online.itp.ucsb.edu/online/qhalLc98/dekker/. Transmission electron microscopy image of multi-wall carbon nanotube (MWCNT) treated with iodinated and platinate DNA. The figure was taken from [24] with kind permission from Prof. P. Sadler...

Comparison of CD spectra and 31P NMR spectra of both platinated DNA from several sources and the platinated ds decanucleotide, strongly suggets similar distortions in both cases. Molecular dynamics calculations by Kozelka et al. (64c), based on the above-mentioned decanucleotide, indicated that this kinklike structure can indeed exist. Just as in the crystals of the cts-Pt adduct of d(pGpG), an NH3—OPO3 hydrogen bond appears to be present in the calculated ds decanucleotide structure. 

Comparison of CD spectra and 31P NMR spectra of platinated DNA (from several sources) and the platinated ds decanucleotide, strongly suggests similar distortions in both cases87,94, 101). 

The formation of intrastrand crosslinks on GG and AG base sequences in DNA could be deduced from the presence of the adducts ds-Pt(NH3)2(d(pGG)) and cis-Pt(NH3)2(d(pAG)) in digests of platinated DNA. However, no indications for the presence of GA adducts could be found, and therefore crosslinks with a GA sequence are unlikely. 

It now appears153 that interindividual human variations in cisplatin response can be detected with an in vitro assay. Lippard et al.159 have reported that site-specifically platinated DNA is a new probe for the biological activity of cisplatin. 

Findings with platinated DNA fragments (107-109) confirm the acidification of guanine residues upon N7 Pt coordination. In fact, changes in proton NMR (JH NMR) chemical shifts of guanine-H8 resonances are commonly used to assign binding sites in DNA. 

In order to understand all aspects of the action of cisplatin as an anticancer agent, further structural research on the complexes between HMG-domain proteins and platinated DNA fragments will be necessary. On the other hand, further studies of small model compounds may furnish several new details of the chemistry controlling cisplatin-DNA interactions. 

Figure 14 Stereoviews of the NMR solution structures of platinated DNA sequences iUiistrating the deformation of the normal double-helical structure, (a) intrastrand cis-GG crosslink in d(CCTCTG G TCTCC)-d(GGAGACCAGAGG) (b) interstrand cis-GG crosslink in the palindromic sequence d(CATAG CTATG)-d(CATAG CTATG) represents the donor nucleotides. (Reprinted with permission from Ref 90. 1999 American Chemical Society)...

The high mobility group (HMG) proteins can recognize the bend on the platinated DNA a-helix and bind to it.2 Structures of such Pt-DNA-HMG complexes were solved recently based on crystallographic data.3 5... 

---