Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex

HOFR, Ctirad, Nicholas FARRELL and Viktor BRABEC. Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex. Nucleic Acids Research. Oxford, UK: Oxford Press, 2001, vol. 29, No 10, p. 2034-2040. ISSN 0305-1048.

Basic information

• Original name: Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex
• Authors: HOFR, Ctirad, Nicholas FARRELL and Viktor BRABEC.
• Edition: Nucleic Acids Research, Oxford, UK, Oxford Press, 2001, 0305-1048.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10610 Biophysics
• Country of publisher: Czech Republic
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 6.373
• RIV identification code: RIV/00216224:14310/01:00004214
• Organization unit: Faculty of Science
• Keywords in English: DNA; thermodynamic stability; platinum drugs; calorimetry
• Tags: calorimetry, DNA, platinum drugs, thermodynamic stability

Abstract

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.

Links

• GA305/99/0695, research and development project: Name: Ovlivnění konformace DNA protinádorově účinnými komplexy kovů. Vztah k vývoji nových cytostatik.