Detailed Information on Publication Record
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 BRABECBasic 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
Tags
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 |
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