Synthesis and thermodynamic analysis of a cisplatin-modified DNA 12-mey

Cisplatin, cis-[PtCl2(NH3)2], is an anti-cancer drug that can be used in the treatment of various types of cancer (e.g. testicular cancer). After cisplatin enters the cell and is hydrolysed, it can bind with purine N-7 atoms and form 1,2-intrastrand crosslinks with DNA (Figure 1, right). This binding causes structural changes in DNA and leads to apoptosis of cancer cells. My current research has two main goals: (1) examining the thermodynamic stability of both a control DNA 12-mer duplex and a 12-mer cisplatin-modified DNA duplex (Figure 1, left) by using melting curves obtained with UV/Vis spectroscopy, and (2) examining the thermal stability of individual DNA base pairs of both a control DNA 12-mer and a 12-mer cisplatin-modified DNA using the imino region peaks in 1D 1H NMR. My results will provide important information about how cisplatin binding affects the stability of the DNA duplex, and perhaps lead to a better understanding of how platinum-based drugs are able to kill cancer cells