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Reaction of cis‐diamminedichloroplatinum (II) and DNA in B or Z conformation.
Author(s) -
Malinge J.M.,
Leng M.
Publication year - 1984
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1984.tb01962.x
Subject(s) - guanine , adduct , dna , nuclease , stereochemistry , cytosine , hydrolysis , polymer , conformational change , denticity , nucleotide , biology , chemistry , biochemistry , crystallography , gene , organic chemistry , crystal structure
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.