Transplatin ineffectiveness against cancer from a molecular perspective: A single-molecule force-spectroscopy study.

L Oliveira, J M Caquito, M S Rocha

Physical review. E 2020 Jun

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By performing single-molecule force spectroscopy with optical tweezers, we have characterized the interaction between the platinum-based compound transplatin and the DNA molecule, establishing a critical comparison with its isomer cisplatin. While transplatin is ineffective against tumor cells, its isomer is one of the most used drugs in current chemotherapies, and a molecular study on this difference performed at the single-molecule level was lacking until the present work. Our experiments show that transplatin binds DNA under low chloride concentrations (a situation usually found inside many cells) with an equilibrium association binding constant about four orders of magnitude lower than cisplatin. In addition, we have found that, at saturation, transplatin binds preferentially forming interstrand cross links and monoadducts, a situation very different from cisplatin, which forms preferentially intrastrand cross links. Such differences explain the ineffectiveness of transplatin in killing tumor cells. From a physical point of view, the present study advances in using the mechanical properties of the DNA molecule as sensors to evaluate the therapeutic efficiency of drugs.

Citation

L Oliveira, J M Caquito, M S Rocha. Transplatin ineffectiveness against cancer from a molecular perspective: A single-molecule force-spectroscopy study. Physical review. E. 2020 Jun;101(6-1):062412