Optimization of the efficiency of cross-linking Pt" oligonucleotide phosphorothioate complexes to complementary oligonucleotides

We have investigated the efficiency with which Pt" complexes cross-link phosphorothloates of oligonucleotides to complementary DNA targets. The A and G residues 2- 5 bases downstream from the 5'-phosphorothioate group are preferred sites for cross-linking. Replacement of residues in this part of the target by T residues results in greatly decreased cross-linking when cis platinum diammine dichloride (cisPt11) or potassium platinous chloride (K2PtCI4) are used. Trans platinum diammine dichloride (transPf1) forms cross-links with T residues if A and G residues are absent from the susceptible region of the target. Oligomers containing an internal phosphorothioate group can also be linked to their templates with transPt", but not with cisPt " or K2PtCI4. Cross-linking via an internal phosphorothioate group tends to be less efficient than cross-linking via a 5'-terminal phosphorothioate. The Sp isomers of internal phosphorothioates are cross-linked more efficiently than the FL Isomers. Preliminary experiments suggest that the efficiency of cross-linking to RNA targets will prove similar to that found for DNA targets