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New class of supramolecular complexes bind to DNA

For three decades, continuing problems with resistance and toxic side effects from chemotherapy has stimulated extensive research to create alternative drugs and drug delivery systems to treat cancer. Virginia Tech researchers have had initial success with a new class of supramolecular complexes that could join the arsenal of cancer treatments in the future.

A supramolecular complex is a large molecule composed of two or more smaller molecules, in which the smaller molecules may retain some of their original properties. Complexes of this type have been intensely developed for possible applications as molecular devices and catalysts. Virginia Tech researchers have created a new class of supramolecular complexes that bind to DNA, which will be the subject of papers and posters at the 220th national meeting of the American Chemical Society Aug. 20-24 in Washington, D.C.

Matthew Milkevitch, who received his Ph.D. in chemistry this summer, explains, "Weve developed a supramolecular complex that binds to DNA, is water soluble, and can be easily changed synthetically."

The approach involves coupling the active site of the anticancer drug cisplatin (cis-diamminedichoroplatinum(II)) to a ruthenium(II) chromophore. Cisplatin produces its therapeutic effects through binding to cellular DNA, disrupting normal cell division. Several ruthenium(II) chromophores have been shown in the literature to bind to DNA by intercalation (inserting a portion of the molecule between the base pairs of the DNA helix).

But the most novel aspect of the supramolecular complexes is that the scientists can change the parts of the complex in a straight-forward fashion. "This ability has allowed us to make a series of complexes and to determine how the parts of the complex effect DNA binding," Milkevitch says.

An analogy might be the development of a race car. "To produce a competitive car, different engine, suspension, tire, and braking setups
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Contact: Dr. Karen Brewer
kbrewer@chemserver.chem.vt.edu
540-231-6579
Virginia Tech
20-Aug-2000


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