Publication details

Steric control of DNA interstrand cross-link sites of trans platinum complexes: specificity can be dictated by planar nonleaving groups

Authors

BRABEC Viktor NEPLECHOVÁ Kamila KAŠPÁRKOVÁ Jana FARRELL Nicholas

Year of publication 2000
Type Article in Periodical
Magazine / Source Journal of Biological Inorganic Chemistry
MU Faculty or unit

Faculty of Science

Citation
Field Biophysics
Description Recent findings that novel trans-dichloroplatinum(II) complexes exhibit antitumor activity violate the classical structure-activity relationships of platinum(II) complexes. These novel "nonclassical" trans-platinum complexes also comprise those containing planar aromatic amines. The initial studies have shown that these compounds form a considerable amount of DNA interstrand cross-links (up to ~30 %) with a rate markedly higher than clinically ineffective transplatin. The present work has shown that DNA interstrand cross-linking by trans-[PtCl2(NH3)(quinoline)] and trans-[PtCl2(NH3)(thiazole)] is formally equivalent to that by antitumor cisplatin, but different from clinically ineffective transplatin which preferentially forms these adducts between complementary guanine and cytosine residues. This result shows for the first time that the simple chemical modification of structure of an inactive compound alters its DNA binding site into a DNA adduct of an active drug.

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

More info