Oligonucleotides modified with transplatin derivatives: fast and efficient metalloribozymes

When an oligonucleotide containing a 1,3-(G,G)-transplatin cross-link at a GNG site (N represents a C, T, A or U residue) is paired with its complementary strand, the intrastrand adduct rearranges into an interstrand cross-link, resulting in the covalent attachment of both strands. Here, we have studied the influence of the inert ligands of the platinum(II) complex and of the nucleotide residues in the vicinity of the adduct on the rearrangement reaction. Dramatic effects on the linkage isomerization rate could be 37. The results are analyzed in relation with the mechanism of rearrangement of the 1,3-intrastrand adducts into interstrand cross-links. The relevance of platinated oligonucleotides as potent and specific drugs is discussed.