0399443 - BFÚ 2014 RIV DE eng J - Journal Article
Malina, Jaroslav - Natile, G. - Brabec, Viktor
Spontaneous Translocation of Antitumor Oxaliplatin, its Enantiomeric Analogue, and Cisplatin from One Strand to Another in Double-Helical DNA.
Chemistry - A European Journal. Roč. 19, č. 36 (2013), s. 11984-11991. ISSN 0947-6539. E-ISSN 1521-3765
R&D Projects: GA ČR(CZ) GAP205/11/0856; GA ČR(CZ) GAP301/10/0598
Institutional support: RVO:68081707
Keywords : antitumor agents * calorimetry * DNA
Subject RIV: BO - Biophysics
Impact factor: 5.696, year: 2013 ; AIS: 1.406, rok: 2013
DOI: https://doi.org/10.1002/chem.201300946

Oxaliplatin and cisplatin belong to the class of platinum-based anticancer agents. Formation of DNA adducts by these complexes and the consequences for its structure and function, is the mechanistic paradigm by which these drugs exert their antitumor activity. We show that employing short oligonucleotide duplexes containing single, site-specific 1,3-intrastrand cross-links of oxaliplatin, its enantiomeric analogue, or cisplatin and by using gel electrophoresis that under physiological conditions the coordination bonds between platinum and the N7 position of guanine residues involved in the cross-links of the Pt-II complexes can be cleaved. This cleavage may lead to linkage isomerization reactions between these metallodrugs and double-helical DNA. For instance, approximately 25% 1,3-intrastrand cross-links of the platinum complexes isomerized after 192h (at 310K in 200mM NaClO4).
Permanent Link: http://hdl.handle.net/11104/0226773