title: Evidence for similar structural changes on binding of platinum anti-tumor agents to DNA and nucleosomes.
abstract: The influence of Pt(II) compounds on the 31P NMR spectra of natural DNA, synthetic polynucleotides, and nucleosomes was investigated. With Pt complexes which are anti-tumor agents, a new peak or shoulder centered at approximately 1.2 ppm downfield from the untreated DNA signal was observed. When Pt compounds known not to be anti-tumor agents were studied, no such new signal was observed. The most reasonable explanation for the downfield resonance is that it is a consequence of a structural change induced in the DNA by the anti-tumor agent. Since the effect of the Pt compounds on nucleosomes was similar, the same structural change is probably occurring in DNA in solution and in nucleosomes. A nonalternating dG . dC polymer, but not alternating G . C or any A . T polymers, exhibited a similar spectral change and this finding suggests that the structural change in the DNA arises primarily from reaction of Pt anti-tumor agents with adjacent G residues.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009707:Nucleosomes / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D012474:Salmon; D013094:Spermatozoa / Q000032:analysis; D013950:Thymus Gland / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D009707:Nucleosomes; D009944:Organoplatinum Compounds; C002892:platinum ethylenediamine dichloride; D004247:DNA; D002945:Cisplatin