Transplatin-modified oligonucleotides as modulators of gene expression.
Transplatin [trans-diamminedichloroplatinum(II)], contrary to its stereoisomer cisplatin, is clinically inactive. However, like cisplatin, it binds to DNA. In the first part of this review, some results on the interactions between transplatin and double-stranded DNA are presented. The major bifunctional adducts are interstrand cross-links. Intrastrand cross-links are not formed. On the other hand, intrastrand cross-links are formed in the reaction between single-stranded DNA and transplatin. Some properties of the intrastrand cross-links at GNG sites (N is a nucleotide) are described. The (G1,G3)-intrastrand cross-links rearrange into interstrand cross-links as soon as the platinated oligonucleotides are paired with their complementary strands. The linkage isomerization reaction is exclusively triggered by the formation of a double helix. The potential use of these platinated oligonucleotides to block the cellular machinery specifically and irreversibly is discussed.
Giraud-Panis
M
M
Centre de Biophysique Moléculaire, CNRS, Rue Charles Sadron, 45071, Orléans, France.
Leng
M
M
D001665:Binding Sites; D002945:Cisplatin / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009841:Oligonucleotides / Q000378:metabolism*
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D009841:Oligonucleotides; C034697:transplatin; D004247:DNA; D002945:Cisplatin