Raman spectroscopy of DNA modified by intrastrand cross-links of antitumor cisplatin.
Raman spectroscopy was employed to characterize the perturbations to DNA conformation induced in DNA by two different intrastrand adducts of antitumor cis-diamminedichloroplatinum(II) (cisplatin), namely by its 1,2-GG or 1,3-GTG intrastrand cross-links. We examined short deoxyribooligonucleotide duplexes containing single, site-specific cross-link by Raman spectroscopy and assigned the spectral alterations to conformational changes induced in DNA by 1,2-GG or 1,3-GTG intrastrand CLs determined earlier by other biochemical and biophysical methods. The results confirmed significant perturbations to the B-form DNA backbone due to the intrastrand lesions and that several nucleotides changed their conformation from C2'-endo to C3'-endo. Evidence for a partial transition from B- to A-form was found in several regions of the Raman spectra as well. The spectra also confirmed the different and more extensive distortion induced in B-DNA by 1,3-GTG in comparison with 1,2-GG intrastrand CLs, consistent with their already known high resolution structures. The results of the present work demonstrate that Raman spectroscopy represents a suitable tool to provide insights into structural factors involved in the mechanisms underlying antitumor effects of platinum drugs.
Vrána
Oldrich
O
Institute of Biophysics, Academy of Sciences of the Czech Republic, Kralovopolska 135, CZ-61265 Brno, Czech Republic.
Masek
Vlastimil
V
Drazan
Viktor
V
Brabec
Viktor
V
D000970:Antineoplastic Agents; D002945:Cisplatin / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004247:DNA / Q000737:chemistry*; D044704:DNA, A-Form; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013059:Spectrum Analysis, Raman
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D044704:DNA, A-Form; D004247:DNA; D002945:Cisplatin