Effects of Monofunctional Adducts of Platinum(II) Complexes on Thermodynamic Stability and Energetics of DNA Duplexes
Vendula Bursova 1, Jana Kasparkova 1, Ctirad Hofr 2 and Viktor Brabec 3*
1 Institute of Biophysics AS CR, Brno
2 Institute of Biophysics AS CR, Brn
3 Institute of Biophysics, Academy of Sciences of the Czech Republic
* To whom correspondence should be addressed. E-mail: brabec{at}ibp.cz.
Submitted on August 23, 2004
Revised on October 4, 2004
Accepted on 19 November 2004
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Abstract |
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Effects of adducts of [PtCl(NH3)3]Cl or chlorodiethylenetriamineplatinum(II) on DNA stability were studied with emphasis on thermodynamic origins of that stability. 15-bp oligodeoxyribonucleotide duplexes containing the single, site-specific monofunctional adduct at G residues of the central sequences TGT/ACA or 5'-AGT/5'-ACT were prepared and analyzed by differential scanning calorimetry, temperature-dependent UV absorption and circular dichroism. The unfolding of the platinated duplexes was accompanied by relatively small unfavorable free energy terms. This destabilization was enthalpic in origin. On the other hand, a relatively large reduction of melting temperature (Tm) was observed as a consequence of the monofunctional adduct in the TGT sequence, whereas Tm due to the adduct in the AGT sequence was reduced only slightly. We also examined the efficiency of the mammalian nucleotide excision repair system to remove from DNA the monofunctional adducts and found that these lesions were not recognized by this repair system. Thus, rather thermodynamic than thermal characterization of DNA adducts of monofunctional platinum compounds is a property implicated in the modulation of downstream effects such as protein recognition and repair.
Key Words:
DNA, calorimetry, circular dichroism, nucleotide excision repair, platinum complexes
