Monofunctional adducts of platinum(II) produce in DNA a sequence-dependent local denaturation.
The effects on the conformation of DNA produced by the monofunctional adducts of chloro-(diethylenetriamine)platinum(II) chloride or cis-diamminemonoaquamonochloroplatinum(II) have been investigated by means of the single-strand-specific probe chloroacetaldehyde (CAA). The denatured sites to which CAA was bound and that were induced in DNA by the monofunctional adducts of the platinum complexes were characterized by means of three experimental approaches. These include measurement of the fluorescence of a plasmid fragment treated with CAA, analysis of oligonucleotides treated with CAA and cleaved by piperidine, and termination of duplex transcription on a fragment of plasmid DNA treated with CAA. The results indicate that the denaturational change preferentially occurs in the base pair containing the monoadducted deoxyriboguanosine in the trinucleotide sequence Py-deoxyriboguanosine-Py (Py is a pyrimidine deoxyribonucleoside). It was suggested that this conformational alteration facilitates in DNA the formation of minor bifunctional adducts of cis-diamminedichloroplatinum(II).
Brabec
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Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno.
Boudný
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Balcarová
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D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D001482:Base Composition; D001483:Base Sequence; D002874:Chromosome Mapping; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific; D004797:Enzyme-Linked Immunosorbent Assay; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009691:Nucleic Acid Denaturation / Q000187:drug effects*; D010880:Piperidines / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014158:Transcription, Genetic
D010880:Piperidines; C078724:diamminemonoaquamonochloroplatinum(II); C032799:chlorodiethylenetriamine platinum; C032727:piperidine; D004247:DNA; C004656:chloroacetaldehyde; C024406:endodeoxyribonuclease HpaI; C037106:endodeoxyribonuclease NdeI; D015252:Deoxyribonucleases, Type II Site-Specific; D000079:Acetaldehyde; D002945:Cisplatin