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@article{837295,
author = {Marini Palomeque, María Victoria and Christofis, Petros and Nováková, Olga and Kašpárková, Jana and Farrell, Nicholas and Brabec, Viktor},
article_location = {UK},
article_number = {18},
keywords = {platinum complexes; DNA; antitumor},
language = {eng},
issn = {0305-1048},
journal = {Nucleic Acids Research},
title = {Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)]},
volume = {33},
year = {2005}
}
TY - JOUR
ID - 837295
AU - Marini Palomeque, María Victoria - Christofis, Petros - Nováková, Olga - Kašpárková, Jana - Farrell, Nicholas - Brabec, Viktor
PY - 2005
TI - Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)]
JF - Nucleic Acids Research
VL - 33
IS - 18
SP - 5819–5828
EP - 5819–5828
PB - Oxford University Press
SN - 03051048
KW - platinum complexes
KW - DNA
KW - antitumor
N2 - Replacement of one ammine in clinically ineffective trans-[PtCl2(NH3)2] (transplatin) by a planar N-heterocycle, thiazole, results in significantly enhanced cytotoxicity. Unlike "classical" cisplatin {cis-[PtCl2(NH3)2]} or transplatin, modification of DNA by this prototypical cytotoxic transplatinum complex trans-[PtCl2(NH3)(thiazole)] (trans-PtTz) leads to monofunctional and bifunctional intra or interstrand adducts in roughly equal proportions. DNA fragments containing site-specific bifunctional DNA adducts of trans-PtTz were prepared. The structural distortions induced in DNA by these adducts and their consequences for high-mobility group protein recognition, DNA polymerization and nucleotide excision repair were assessed in cell-free media by biochemical methods. Whereas monofunctional adducts of trans-PtTz behave similar to the major intrastrand adduct of cisplatin [J. Kasparkova, O. Novakova, N. Farrell and V. Brabec (2003) Biochemistry, 42, 792-800], bifunctional cross-links behave distinctly differently. The results suggest that the multiple DNA lesions available to trans-planaramine complexes may all contribute substantially to their cytotoxicity so that the overall drug cytotoxicity could be the sum of the contributions of each of these adducts. However, acquisition of drug resistance could be a relatively rare event, since it would have to entail resistance to or tolerance of multiple, structurally dissimilar DNA lesions.
ER -
MARINI PALOMEQUE, María Victoria, Petros CHRISTOFIS, Olga NOVÁKOVÁ, Jana KAŠPÁRKOVÁ, Nicholas FARRELL a Viktor BRABEC. Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)]. \textit{Nucleic Acids Research}. UK: Oxford University Press, 2005, roč.~33, č.~18, s.~5819–5828. ISSN~0305-1048.
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