Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.
The nature of the adducts and the conformational changes produced in poly(dG-m5dC).poly(dG-m5dC) by cis-diamminedichloroplatinum(II) (cisPt) have been studied. In the reaction of cisPt and B-DNA, the main adduct is bidentate and arises from an intrastrand cross-link between two guanine residues separated by a cytosine. This was deduced from the study of the compounds by t.l.c. after acid hydrolysis of the polymer. The platinated polymer is not digested by S1 nuclease. The antibodies to Z-DNA bind to the platinated polymer with a smaller affinity than to poly (dG-br5dC).poly(dG-br5dC). The c.d. spectrum differs from that of poly(dG-br5dC).poly(dG-br5dC) or poly(dG-m5dC).poly-(dG-m5dC) in Z conformation. It is concluded that the bidentate adduct induces a conformational change from the B form towards a distorted Z form. In the reaction of cisPt and Z-DNA, a monodentate adduct is formed. This adduct stabilizes the Z conformation as shown by c.d. and binding to the anti-Z-DNA antibodies. At room temperature, the second function of the drug can still react with small ligands such as NH4HCO3. By heating, the second function reacts with a guanine residue. A bidentate adduct is formed as in the reaction of cisPt and B-DNA and it induces a transition from the Z form to the distorted Z form.
D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin; D003596:Cytosine; D004247:DNA; D006147:Guanine; D009690:Nucleic Acid Conformation; D011089:Polydeoxyribonucleotides; D013329:Structure-Activity Relationship; D013950:Thymus Gland
D011089:Polydeoxyribonucleotides; D006147:Guanine; D003596:Cytosine; D004247:DNA; D002945:Cisplatin