Publication details
Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex
| Authors | |
|---|---|
| Year of publication | 2001 |
| Type | Article in Periodical |
| Magazine / Source | Nucleic Acids Research |
| MU Faculty or unit | |
| Citation | |
| Field | Biophysics |
| Keywords | DNA; thermodynamic stability; platinum drugs; calorimetry |
| Description | Bifunctional polynuclear platinum compounds represent a novel class of metal-based antitumor drugs. A typical agent is [{trans-PtCl(NH3)2}2H2N(CH2)4NH2]Cl2, (1,1/t,t) which coordinates to bases in DNA and forms covalent cross-links. It also forms a 1,2-d(GpG) intrastrand adduct, the equivalent of the major DNA lesion of "classical" cisplatin. In the present study, differential scanning calorimetry and spectroscopic techniques were employed to characterize the influence of this cross-link on the thermal stability and energetics of 20 bp DNA duplexes site-specifically modified by 1,1/t,t. Thermal denaturation data revealed that the cross-link of 1,1/t,t reduced thermal and thermodynamical stability of the duplex noticeably more than that of "classical" cisplatin. The energetic consequences of the intrastrand cross-link at the d(GG) site are discussed in relation to the structural distortions induced by this adduct in DNA and to its recognition and binding by HMG-domain proteins. |