New Molecule Binds to Cancer’s DNA, Prevents Replication

March 2nd, 2015 Editors News

Researches at Bielefeld University in Germany have come upon a new method of disrupting the spread of cancer using molecules that bind to DNA. The team developed a synthetic molecule that has two ions of copper at one end. The copper ions are attracted to the phosphate components of the DNA, binding to the large molecule and altering its functionality. The attached molecule alters the ability of a cell to use the DNA correctly, causing it to make errors while preventing the normal copying of the genetic material.

The team initially confirmed that the new molecule binds to DNA and prevents the replication of the genome. They then tested the molecule on actual cancer cells, demonstrating that its more effective at killing them than the popular cisplatin chemo drug.

From the study in journal Inorganic Chemistry:

The mechanism of the cytotoxic function of cisplatin and related anticancer drugs is based on their binding to the nucleobases of DNA. The development of new classes of anticancer drugs requires establishing other binding modes. Therefore, we performed a rational design for complexes that target two neighboring phosphates of the DNA backbone by molecular recognition resulting in a family of dinuclear complexes based on 2,7-disubstituted 1,8-naphthalenediol. This rigid backbone preorganizes the two metal ions for molecular recognition at the distance of two neighboring phosphates in DNA of 6-7 Å. Additionally, bulky chelating pendant arms in the 2,7-position impede nucleobase complexation by steric hindrance. We successfully synthesized the Cu^II₂ complex of the designed family of dinuclear complexes and studied its binding to dsDNA by independent ensemble and single-molecule methods like gel electrophoresis, precipitation, and titration experiments followed by UV-vis spectroscopy, atomic force microscopy (AFM), as well as optical tweezers (OT) and magnetic tweezers (MT) DNA stretching. The observed irreversible binding of our dinuclear Cu^II₂ complex to dsDNA leads to a blocking of DNA synthesis as studied by polymerase chain reactions and cytotoxicity for human cancer cells.

Study in Inorganic Chemistry: Rational Design of a Cytotoxic Dinuclear Cu2 Complex That Binds by Molecular Recognition at Two Neighboring Phosphates of the DNA Backbone…

Source: Bielefeld University…

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