Biophysical Studies on the Stability of DNA Intrastrand
Cross-Links of Transplatin

J 2008

Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin

KAŠPÁRKOVÁ, Jana, María Victoria MARINI PALOMEQUE, Vendula BURSOVÁ and Viktor BRABEC

Basic information

Original name

Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin

Name in Czech

Biofyzikální analýza stability vnitrořetězcových můstků transplatiny na DNA

Authors

KAŠPÁRKOVÁ, Jana (203 Czech Republic, guarantor, belonging to the institution), María Victoria MARINI PALOMEQUE (858 Uruguay, belonging to the institution), Vendula BURSOVÁ (203 Czech Republic, belonging to the institution) and Viktor BRABEC (203 Czech Republic, belonging to the institution)

Edition

Biophysical Journal, USA, Biophysical Society, 2008, 0006-3495

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.683

RIV identification code

RIV/00216224:14310/08:00035832

Organization unit

Faculty of Science

UT WoS

000260072600028

Keywords in English

transplatin; DNA; antitumor

Abstract

ORIG CZ

V originále

Clinically ineffective transplatin [trans-diamminedichloridoplatinum(II)] is used in the studies of the structure-pharmacological activity relationship of platinum compounds. In addition, a number of transplatin analogs exhibit promising toxic effects in several tumor cell lines including those resistant to conventional antitumor cisplatin. Moreover, transplatin-modified oligonucleotides have been shown to be effective modulators of gene expression. Owing to these facts and because DNA is also considered the major pharmacological target of platinum complexes, interactions between transplatin and DNA are of great interest. We examined, using biophysical and biochemical methods, the stability of 1,3-GNG intrastrand cross-links (CLs) formed by transplatin in short synthetic oligodeoxyribonucleotide duplexes and natural double-helical DNA. We have found that transplatin forms in double-helical DNA 1,3-GNG intrastrand CLs, but their stability depends on the sequence context. In some sequences the 1,3-GNG intrastrand CLs formed by transplatin in double-helical DNA readily rearrange into interstrand CLs. On the other hand, in a number of other sequences these intrastrand CLs are relatively stable. We show that the stability of 1,3-GNG intrastrand CLs of transplatin correlates with the extent of conformational distortion and thermodynamic destabilization induced in double-helical DNA by this adduct.

In Czech

Klinicky neúčinná transplatina je předmětem studií vztahů struktury a farmakologické aktivity platinových komplexů.

Links

LC06030, research and development project

Name: Biomolekulární centrum

Investor: Ministry of Education, Youth and Sports of the CR, Biomolecular centre

Citovat

KAŠPÁRKOVÁ, Jana, María Victoria MARINI PALOMEQUE, Vendula BURSOVÁ and Viktor BRABEC. Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin. Biophysical Journal. USA: Biophysical Society, 2008, vol. 95, No 9, p. 4361-4371. ISSN 0006-3495.

@article{837278,
   author = {Kašpárková, Jana and Marini Palomeque, María Victoria and Bursová, Vendula and Brabec, Viktor},
   article_location = {USA},
   article_number = {9},
   keywords = {transplatin; DNA; antitumor},
   language = {eng},
   issn = {0006-3495},
   journal = {Biophysical Journal},
   title = {Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin},
   volume = {95},
   year = {2008}
}

TY  - JOUR
ID  - 837278
AU  - Kašpárková, Jana - Marini Palomeque, María Victoria - Bursová, Vendula - Brabec, Viktor
PY  - 2008
TI  - Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin
JF  - Biophysical Journal
VL  - 95
IS  - 9
SP  - 4361-4371
EP  - 4361-4371
PB  - Biophysical Society
SN  - 00063495
KW  - transplatin
KW  - DNA
KW  - antitumor
N2  - Clinically ineffective transplatin [trans-diamminedichloridoplatinum(II)] is used in the studies of the structure-pharmacological activity relationship of platinum compounds. In addition, a number of transplatin analogs exhibit promising toxic effects in several tumor cell lines including those resistant to conventional antitumor cisplatin. Moreover, transplatin-modified oligonucleotides have been shown to be effective modulators of gene expression. Owing to these facts and because DNA is also considered the major pharmacological target of platinum complexes, interactions between transplatin and DNA are of great interest. We examined, using biophysical and biochemical methods, the stability of 1,3-GNG intrastrand cross-links (CLs) formed by transplatin in short synthetic oligodeoxyribonucleotide duplexes and natural double-helical DNA. We have found that transplatin forms in double-helical DNA 1,3-GNG intrastrand CLs, but their stability depends on the sequence context. In some sequences the 1,3-GNG intrastrand CLs formed by transplatin in double-helical DNA readily rearrange into interstrand CLs. On the other hand, in a number of other sequences these intrastrand CLs are relatively stable. We show that the stability of 1,3-GNG intrastrand CLs of transplatin correlates with the extent of conformational distortion and thermodynamic destabilization induced in double-helical DNA by this adduct.
ER  -

KAŠPÁRKOVÁ, Jana, María Victoria MARINI PALOMEQUE, Vendula BURSOVÁ and Viktor BRABEC. Biophysical Studies on the Stability of DNA Intrastrand Cross-Links of Transplatin. \textit{Biophysical Journal}. USA: Biophysical Society, 2008, vol.~95, No~9, p.~4361-4371. ISSN~0006-3495.

Detailed Information on Publication Record