ZEHNULOVÁ, Jana, Jana KAŠPÁRKOVÁ, Nicholas FARRELL and Viktor BRABEC. Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol., vol. 276, No 25, p. 22191-22199. ISSN 0021-9258. 2001.
Other formats:   BibTeX LaTeX RIS
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
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: 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 anticancer drug, conformation, DNA, platinum, recognition
Changed by Changed by: prof. RNDr. Viktor Brabec, DrSc., učo 46787. Changed: 2/7/2001 12:08.
Abstract
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 projectName: Ovlivnění konformace DNA protinádorově účinnými komplexy kovů. Vztah k vývoji nových cytostatik.
PrintDisplayed: 18/4/2024 21:32