Effects of monofunctional adducts of platinum(II) complexes on thermodynamic stability and energetics of DNA duplexes.

Abstract:

: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 (T(m)) was observed as a consequence of the monofunctional adduct in the TGT sequence, whereas T(m) 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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Bursova V,Kasparkova J,Hofr C,Brabec V

doi

10.1529/biophysj.104.051771

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

1207-14

issue

2

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(05)73187-8

journal_volume

88

pub_type

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