J 2000

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

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

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: 3.045

RIV identification code

RIV/00216224:14310/00:00003310

Organization unit

Faculty of Science
Změněno: 27/2/2001 10:02, prof. RNDr. Viktor Brabec, DrSc.

Abstract

V originále

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.