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

BRABEC, Viktor, Kamila NEPLECHOVÁ, Jana KAŠPÁRKOVÁ and Nicholas FARRELL. Steric control of DNA interstrand cross-link sites of trans platinum complexes: specificity can be dictated by planar nonleaving groups. Journal of Biological Inorganic Chemistry. Germany: Springer-Verlag, 2000, vol. 2000, No 5, p. 364-368. ISSN 0949-8257.

Basic information

• Original name: Steric control of DNA interstrand cross-link sites of trans platinum complexes: specificity can be dictated by planar nonleaving groups
• Authors: BRABEC, Viktor, Kamila NEPLECHOVÁ, Jana KAŠPÁRKOVÁ and Nicholas FARRELL.
• Edition: Journal of Biological Inorganic Chemistry, Germany, Springer-Verlag, 2000, 0949-8257.

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: 3.045
• RIV identification code: RIV/00216224:14310/00:00003310
• Organization unit: Faculty of Science

Abstract

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.

Links

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