Interaction between anticancer drugs and DNA studied by using electrospray ionization mass spectrometry / 药学学报

ABSTRACT

To elucidate further sequence selectivity and nature of the binding of anticancer drugs to DNA, the interaction between anticancer drugs, which are minor groove ligands (distamycin A, DM and netropsin, NP) and intercalator (mitoxantrone, MT), and DNA were studied by electrospray ionization mass spectrometry. The 2 1 specific complex of DM and AT-rich DNA were observed principally, while only 1 1 specific complex of NP and AT-rich DNA were observed. MT specifically binds to GC-rich DNA. In addition, DM binds to DNA containing 5 A/T bases minor groove almost in a 2 1 mode and does not bind to DNA containing 3 A/T bases minor groove. NP binds most strongly to DNA containing 4 A/T bases minor groove. The 1 1 specific complex of MT and 6-mer DNA was also observed. The result of competitive binding experiment shows that DM binds more strongly to AT-rich DNA than NP does. These results provide bases for investigating the mechanism of interaction between the drugs and DNA and for improving the structure of target drug.