J 2001

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

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Změněno: 25/5/2001 15:21, prof. RNDr. Viktor Brabec, DrSc.

Abstract

V originále

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.