J 2001

Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464

ZEHNULOVÁ, Jana, Jana KAŠPÁRKOVÁ, Nicholas FARRELL and Viktor BRABEC

Basic information

Original name

Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464

Authors

ZEHNULOVÁ, Jana, Jana KAŠPÁRKOVÁ, Nicholas FARRELL and Viktor BRABEC

Edition

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. 2001, 0021-9258

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: 7.258

RIV identification code

RIV/00216224:14310/01:00004290

Organization unit

Faculty of Science

Keywords in English

DNA; anticancer drug; platinum; conformation; recognition
Změněno: 2/7/2001 12:08, prof. RNDr. Viktor Brabec, DrSc.

Abstract

V originále

The new antitumor trinuclear platinum compound [{trans-PtCl(NH3)2}2m- trans-Pt(NH3)2{H2N(CH2)6NH2}2]4+ (designated as BBR3464) is currently in Phase II clinical trials. DNA is generally considered the major pharmacological target of platinum drugs. The bifunctional DNA binding of BBR3464 is characterized by the rapid formation of long-range intra- and interstrand cross-links. We examined how the structures of the various types of the intrastrand cross-links of BBR3464 affect conformational properties of DNA, how these adducts are recognized by HMG1 protein and removed from DNA during in vitro nucleotide excision repair reactions. The results have revealed that intrastrand cross-links of BBR3464 create a local conformational distortion, but none of these cross-links results in a stable curvature. In addition, we have observed no recognition of these cross-links by HMG1 proteins, but we have observed effective removal of these adducts from DNA by nucleotide excision repair.

Links

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