Transplatin-modified oligonucleotides as modulators of gene expression

Transplatin [trans-diamminedichloroplatinum(II)], contrary to its stereoiso mer cisplatin, is clinically inactive. However, like cisplatin, it binds to DNA. In the first part of this review, some results on the interactions be tween transplatin and double-stranded DNA are presented. The major bifuncti onal adducts are interstrand cross-links. Intrastrand cross-links are not f ormed. On the other hand, intrastrand cross-links are formed in the reactio n between single-stranded DNA and transplatin. Some properties of the intra strand 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 stra nds. The linkage isomerization reaction is exclusively triggered by the for mation of a double helix. The potential use of these platinated oligonucleo tides to block the cellular machinery specifically and irreversibly is disc ussed. (C) 2000 Elsevier Science Inc. All rights reserved.