Raman spectroscopic evaluation of DNA adducts of a platinum containing anticancer drug

• Carboplatin cross-links DNA bases which are essentially covalent modifications.
• Two adjacent guanines and adjacent guanine–adenine residues should be involved in platination of DNA by carboplatin.
• Such covalent cross-links of DNA bases result in kinking and bending of the DNA.
• These distortional modifications of DNA result in perturbation of native B-DNA conformation, forming basis of cell death.

Mechanistic understanding of the interaction of drugs with their target molecules is important for better understanding of their mode of action and to improve their efficacy. Carboplatin is a platinum containing anticancer drug, used to treat different type of tumors. In the present work, we applied Raman spectroscopy to study the interaction of carboplatin with DNA at molecular level using different carboplatin–DNA molar ratios. These Raman spectroscopic results provide comprehensive understanding on the carboplatin–DNA interactions and indicate that DNA cross-linked adducts formed by carboplatin are similar to cisplatin adducts. The results indicate that guanine N7 and adenine N7 are the putative sites for carboplatin interaction. It is observed that carboplatin has some affinity toward cytosine in DNA. Phosphate sugar backbone of DNA showed conformation perturbation in DNA which were easily sensible at higher concentrations of carboplatin. Most importantly, carboplatin interaction induces intermediate A- and B-DNA conformations at the cross-linking sites.

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