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@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.
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