News Release

New class of supramolecular complexes bind to DNA

Peer-Reviewed Publication

Virginia Tech

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, "We’ve 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 must be studied in order to maximize the car’s performance. This same idea is achieved in our supramolecular complexes by removing and replacing parts of complex to study how it changes how the complex binds to DNA."

The second goal of this research was to develop methods to detect and study the DNA binding of these supramolecular complexes. "Working with Dr. Brenda S.J. Winkel, a faculty member in biology, we developed a series of assays to do that," Milkevitch says.

This new class of supramolecular complexes absorbs light throughout the ultraviolet and visible range, a property that the researchers hope to exploit to further study their interactions with DNA. "Where the complexes absorb light may change upon DNA binding," Milkevitch says.

A poster by Milkevitch, Winkel, and chemistry professor Karen Brewer on "Interaction of Ruthenium-Platinum Bimetallic Complexes with DNA" (INOR 130) will be presented Sunday, Aug. 20, at 7 p.m. in Convention Center Exhibit Hall D as part of the inorganic chemistry program, and has been selected to be presented again Monday at 8 p.m. in the same location during the mixed science (Sci-Mix) poster session.

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A paper by R. Lee Williams, Milkevitch, and Brewer on "Ruthenium-Platinum Polypyridyl Complexes: Synthesis, Characterization and DNA Binding" (INOR 516) will be presented at 11 a.m. Thursday, Aug. 24, at the Renaissance Washington Hotel, room Renaissance West B, as part of the Transition Metals Symposium. Williams is a master's degree student in chemistry at Virginia Tech. The research is supported by the National Science Foundation and the Carilion Biomedical Institute through Virginia Tech's Optical Sciences and Engineering Research Center.

PR Contact: Susan Trulove
540-231-5646 strulove@vt.edu


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