Molecular mechanics modeling of oligonucleotide adducts of the antitumor drug cis-diamminedichloroplatinum(II)

In order to assess the geometric changes caused when the antitumor drug cis-diammine-dichloroplatinum(II) (cis-DDP) binds to DNA, molecular mechanics calculations were performed on two double-stranded and two single-stranded oligonucleotides and their adducts with cis-{Pt(NH₃)₂}²⁺. For the platinated duplexes, three model structures have been derived, one involving only local disruption of base pairing with retention of the helix directionality, and two models showing pronounced kinking of the double helix. One of the kinked models is stabilized by bridging sodium ions. The other kinked duplex model shows retention of all Watson–Crick base pairing, including that of the coordinated guanines. All models exhibit hydrogen bonds connecting one ammine ligand of platinum with one or two phosphate groups located at the 5′ side of the platinated strand.