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Originally published as Biophys J. BioFAST on December 1, 2004.
doi:10.1529/biophysj.104.051771
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Biophysical Journal 88:1207-1214 (2005)
© 2005 The Biophysical Society

Effects of Monofunctional Adducts of Platinum(II) Complexes on Thermodynamic Stability and Energetics of DNA Duplexes

Vendula Bursova, Jana Kasparkova, Ctirad Hofr and Viktor Brabec

Institute of Biophysics, Academy of Sciences of the Czech Republic, CZ-61265 Brno, Czech Republic

Correspondence: Address reprint requests to Viktor Brabec, Tel.: 420-541-517-148; Fax: 420-541-240-499; E-mail: brabec{at}ibp.cz.

Effects of adducts of [PtCl(NH3)3]Cl or chlorodiethylenetriamineplatinum(II) on DNA stability were studied with emphasis on thermodynamic origins of that stability. Oligodeoxyribonucleotide duplexes (15-bp) 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 ultraviolet 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.






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Copyright © 2005 by the Biophysical Society.