Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F01%3A00004214" target="_blank" >RIV/00216224:14310/01:00004214 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/01:17013005

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex

Popis výsledku v původním jazyce

Bifunctional polynuclear platinum compounds represent a novel class of metal-based antitumor drugs. A typical agent is [{trans-PtCl(NH3)2}2H2N(CH2)4NH2]Cl2, (1,1/t,t) which coordinates to bases in DNA and forms covalent cross-links. It also forms a 1,2-d(GpG) intrastrand adduct, the equivalent of the major DNA lesion of "classical" cisplatin. In the present study, differential scanning calorimetry and spectroscopic techniques were employed to characterize the influence of this cross-link on the thermalstability and energetics of 20 bp DNA duplexes site-specifically modified by 1,1/t,t. Thermal denaturation data revealed that the cross-link of 1,1/t,t reduced thermal and thermodynamical stability of the duplex noticeably more than that of "classical" cisplatin. The energetic consequences of the intrastrand cross-link at the d(GG) site are discussed in relation to the structural distortions induced by this adduct in DNA and to its recognition and binding by HMG-domain proteins.

Název v anglickém jazyce

Thermodynamic properties of duplex DNA containing a site-specific d(GpG) intrastrand crosslink formed by an antitumor dinuclear platinum complex

Popis výsledku anglicky

Bifunctional polynuclear platinum compounds represent a novel class of metal-based antitumor drugs. A typical agent is [{trans-PtCl(NH3)2}2H2N(CH2)4NH2]Cl2, (1,1/t,t) which coordinates to bases in DNA and forms covalent cross-links. It also forms a 1,2-d(GpG) intrastrand adduct, the equivalent of the major DNA lesion of "classical" cisplatin. In the present study, differential scanning calorimetry and spectroscopic techniques were employed to characterize the influence of this cross-link on the thermalstability and energetics of 20 bp DNA duplexes site-specifically modified by 1,1/t,t. Thermal denaturation data revealed that the cross-link of 1,1/t,t reduced thermal and thermodynamical stability of the duplex noticeably more than that of "classical" cisplatin. The energetic consequences of the intrastrand cross-link at the d(GG) site are discussed in relation to the structural distortions induced by this adduct in DNA and to its recognition and binding by HMG-domain proteins.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2001

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nucleic Acids Research

ISSN

0305 1048

e-ISSN

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Svazek periodika

29

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

7

Strana od-do

2034

Kód UT WoS článku

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EID výsledku v databázi Scopus

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