Substitution-Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex-Forming Templates
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
R01 CA078754
NCI NIH HHS - United States
PubMed
29766623
PubMed Central
PMC6625320
DOI
10.1002/anie.201803448
Knihovny.cz E-resources
- Keywords
- DNA polymerase, DNA triplexes, anticancer agents, platinum complexes,
- MeSH
- DNA-Directed DNA Polymerase metabolism MeSH
- DNA drug effects genetics MeSH
- Nucleic Acid Synthesis Inhibitors pharmacology MeSH
- Molecular Structure MeSH
- Organoplatinum Compounds chemical synthesis chemistry pharmacology MeSH
- Polymers chemical synthesis chemistry pharmacology MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Names of Substances
- DNA-Directed DNA Polymerase MeSH
- DNA MeSH
- Nucleic Acid Synthesis Inhibitors MeSH
- Organoplatinum Compounds MeSH
- Polymers MeSH
- triplex DNA MeSH Browser
The formation of triple-helical DNA is implicated in the regulation of gene expression. The triplexes are, however, unstable under physiological conditions so that effective stabilizers for the triplex formation are needed. Herein, we describe a new strategy for the stabilization of such triplexes that is based on antitumor substitution-inert polynuclear platinum complexes (SI-PPCs). These compounds were previously shown to bind to DNA through the phosphate clamp-a discrete mode of DNA-ligand recognition distinct from the canonical intercalation and minor-groove binding. We have found that SI-PPCs efficiently inhibit DNA synthesis by DNA polymerase in sequences prone to the formation of pyrimidine- and purine-motif triplex DNAs. Moreover, the results suggest that SI-PPCs are able to induce the formation of triple-helical DNA between duplexes and strands that are not completely complementary to each other. Collectively, these data provide evidence that SI-PPCs are very efficient stabilizers of triple-stranded DNA that might exert their action by stabilizing higher-order structures such as triple-helical DNA.
Department of Chemistry Virginia Commonwealth University Richmond VA 23284 2006 USA
Institute of Biophysics Czech Academy of Sciences Kralovopolska 135 CZ 61265 Brno Czech Republic
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