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

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 a Viktor BRABEC

Základní údaje

Originální název

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

Autoři

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

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 7.258

Kód RIV

RIV/00216224:14310/01:00004290

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

DNA; anticancer drug; platinum; conformation; recognition

Štítky

anticancer drug, conformation, DNA, platinum, recognition

Změněno: 2. 7. 2001 12:08, prof. RNDr. Viktor Brabec, DrSc.

Anotace

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.

Návaznosti

GA305/99/0695, projekt VaV

Název: Ovlivnění konformace DNA protinádorově účinnými komplexy kovů. Vztah k vývoji nových cytostatik.

Citovat

ZEHNULOVÁ, Jana, Jana KAŠPÁRKOVÁ, Nicholas FARRELL a 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., 2001, roč. 276, č. 25, s. 22191-22199. ISSN 0021-9258.

@article{365796,
   author = {Zehnulová, Jana and Kašpárková, Jana and Farrell, Nicholas and Brabec, Viktor},
   article_location = {Bethesda, USA},
   article_number = {25},
   keywords = {DNA; anticancer drug; platinum; conformation; recognition},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464},
   volume = {276},
   year = {2001}
}

TY  - JOUR
ID  - 365796
AU  - Zehnulová, Jana - Kašpárková, Jana - Farrell, Nicholas - Brabec, Viktor
PY  - 2001
TI  - Conformation, recognition by high mobility group domain proteins, and nucleotide excision repair of DNA intrastrand cross-links of novel antitumor trinuclear platinum complex BBR3464
JF  - Journal of Biological Chemistry
VL  - 276
IS  - 25
SP  - 22191
EP  - 22191
PB  - Amer. Soc. Biochem. Mol.
SN  - 00219258
KW  - DNA
KW  - anticancer drug
KW  - platinum
KW  - conformation
KW  - recognition
N2  - 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.
ER  -

ZEHNULOVÁ, Jana, Jana KAŠPÁRKOVÁ, Nicholas FARRELL a 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. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol., 2001, roč.~276, č.~25, s.~22191-22199. ISSN~0021-9258.

Podrobný výpis o publikaci