Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin

Warning

This publication doesn't include Faculty of Medicine. It includes Faculty of Science. Official publication website can be found on muni.cz.
Authors

KAŠPÁRKOVÁ Jana MARINI PALOMEQUE María Victoria BURSOVÁ Vendula BRABEC Viktor

Year of publication 2008
Type Article in Periodical
Magazine / Source Biophysical Journal
MU Faculty or unit

Faculty of Science

Citation
Field Biophysics
Keywords transplatin; DNA; antitumor
Description Clinically ineffective transplatin [trans-diamminedichloridoplatinum(II)] is used in the studies of the structure-pharmacological activity relationship of platinum compounds. In addition, a number of transplatin analogs exhibit promising toxic effects in several tumor cell lines including those resistant to conventional antitumor cisplatin. Moreover, transplatin-modified oligonucleotides have been shown to be effective modulators of gene expression. Owing to these facts and because DNA is also considered the major pharmacological target of platinum complexes, interactions between transplatin and DNA are of great interest. We examined, using biophysical and biochemical methods, the stability of 1,3-GNG intrastrand cross-links (CLs) formed by transplatin in short synthetic oligodeoxyribonucleotide duplexes and natural double-helical DNA. We have found that transplatin forms in double-helical DNA 1,3-GNG intrastrand CLs, but their stability depends on the sequence context. In some sequences the 1,3-GNG intrastrand CLs formed by transplatin in double-helical DNA readily rearrange into interstrand CLs. On the other hand, in a number of other sequences these intrastrand CLs are relatively stable. We show that the stability of 1,3-GNG intrastrand CLs of transplatin correlates with the extent of conformational distortion and thermodynamic destabilization induced in double-helical DNA by this adduct.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info