MARINI PALOMEQUE, María Victoria, Petros CHRISTOFIS, Olga NOVÁKOVÁ, Jana KAŠPÁRKOVÁ, Nicholas FARRELL and Viktor BRABEC. Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)]. Nucleic Acids Research. UK: Oxford University Press, 2005, vol. 33, No 18, p. 5819–5828. ISSN 0305-1048.
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Basic information
Original name Conformation, protein recognition and repair of DNA interstrand and intrastrand cross-links of antitumor trans-[PtCl2(NH3)(thiazole)]
Name in Czech Konformace, rozpoznani proteiny a oprava DNA retezcovych mustku protinadoroveho trans-[PtCl2(NH3)(thiazol)]
Authors MARINI PALOMEQUE, María Victoria (858 Uruguay), Petros CHRISTOFIS (300 Greece), Olga NOVÁKOVÁ (203 Czech Republic), Jana KAŠPÁRKOVÁ (203 Czech Republic), Nicholas FARRELL (840 United States of America) and Viktor BRABEC (203 Czech Republic, guarantor).
Edition Nucleic Acids Research, UK, Oxford University Press, 2005, 0305-1048.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10610 Biophysics
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 7.552
RIV identification code RIV/00216224:14310/05:00028508
Organization unit Faculty of Science
UT WoS 000233046100024
Keywords (in Czech) platinové komplexy ; DNA; protinadorové
Keywords in English platinum complexes; DNA; antitumor
Tags antitumor, DNA, platinum complexes
Tags International impact, Reviewed
Changed by Changed by: Mgr. María Victoria Marini Palomeque, Ph.D., učo 22912. Changed: 25/3/2010 13:39.
Abstract
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.
Abstract (in Czech)
Nahrazením jedné NH3 skupiny transplatiny planarním N-heterocyklem se značně zvyšuje cytotoxicita.
Links
1QS500040581, research and development projectName: Metalofarmaka, vývoj a mechanismus působení
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