Influence of cis- and trans-diamminedichloroplatinum(II) binding on the helix-coil transition of DNAs with different GC content

The influence of cis-diamminedichloroplatinum(II) (cis-DDP) and trans-diamminedichloroplatinum(II) (trans-DDP) binding on the helix-coil transition of DNAs with different GC composition is investigated experimentally and theoretically (26% ≤ GC ≤ 72%; 0.003 ⩽ rb ⩽ 3; where rb is the number of moles of bound DDP per mole of nucleotide). In contrast to previous studies, it is demonstrated that cis-DDP increases the DNA melting temperature (Tm) if GC content and rb are low enough. Stabilization occurs for rb = 0.003 if GC = 26% or 42%. Destabilization takes place for higher GC and rb values. Trans-DDP causes only stabilization independently of GC content if rb ⩽ 0.3. For the highest GC content (72%), very low concentration rb = 0.003) of both compounds gives rise to a strong shift of the melting temperature which is equal to −4.5°C for cis-DDP and +3.5°C for trans-DDP. It is shown that well known bidentate and monodentate, kinetically inert platinum binding cannot bring about such a strong Tm alteration. Computer simulation of the helix-coil transition of DNA-ligand complexes is used to explain the observed effects.