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PMID: 6540171 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Reaction of cis-diamminedichloroplatinum (II) and DNA in B or Z conformation.

The EMBO journal ·Vol. 3 ·No. 6 ·1984-06-00 ·Pages 1273-9

Malinge JM, Leng M

Abstract

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.

MeSH Terms
Animals Cattle Chemical Phenomena Chemistry Cisplatin Cytosine DNA Guanine Nucleic Acid Conformation Polydeoxyribonucleotides Structure-Activity Relationship Thymus Gland
Chemicals
Polydeoxyribonucleotides Guanine Cytosine DNA Cisplatin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Malinge J M
Leng M
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32 references, click to expand
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1984-06-00
Pages
1273-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557508
Subset
IM
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