Helix-coil transitions in DNA by novel Pt(II) complexes: a pH melting study

Recent reports have shown that pH could also be used as a melting factor to monitor helix-coil transitions in DNA; the results being comparable to those obtained by Tm studies. The rapidity with which the method can be performed to obtain similar transition curves, and elimination of the evaporation factor (at high temperatures as seen in Tm studies) is one of the advantages offered by this technique. With regard to its suitability in studying DNA-drug interactions, the addition of platinum (II) complexes changed the Pm (pH of melting) in a predictable manner thereby confirming the destabilization of bases in DNA. In the present study, melting profiles of calf thymus DNA modified by certain chloro substituted platinum complexes have been generated using pH as a denaturing factor. These novel platinum complexes have been recently shown to have potential tumour inhibiting properties too. Diammine diaqua platinum (active form of the anti tumour drug cisplatin) was coupled to beta poly-L-malate (a bioresorbable polymer synthesized by a myxomycete), L-malate and L-succinate. At a constant Pt:P ratio (0.2), the extent of damage to DNA by these complexes in comparison to cisplatin was cisPt>SuccPt>MalPt>PMA-Pt>carboplatin. Given the similarity of the side groups of these platinum compounds with that of carboplatin (a successful second generation analog of cisplatin), interesting variations have been obtained in the DNA melting profiles, the implications of which have been discussed in the present study.