New 'litmus test' could aid discovery of anti-cancer drugs

EVANSTON, Ill. --- Using the unusual color properties of gold at the nanoscale, scientists at Northwestern University have developed a "litmus test" for DNA and small molecule binding that eventually could be used by pharmaceutical companies to rapidly identify promising candidates for new anti-cancer drugs.

The detection system, called colorimetric screening, can be used to detect a variety of targets, such as DNA, small molecules and proteins, that bind to DNA, and the strength of the bond is indicated by a simple color change.

In a paper reported online today (March 28) by the Journal of the American Chemical Society (JACS), the research team used the colorimetric method to screen for molecules that can facilitate the formation of a special form of DNA called a triple helix. Triple helix DNA involves three strands rather than the two associated with normal DNA. However, unlike double helix DNA, the triple helix is unstable alone and requires a small molecule triplex binder to increase its stability. This research builds on work reported March 6 in the German journal Angewandte Chemie in which the same method was used to screen small molecules for their binding affinity to duplex DNA.

"Pharmaceutical companies are targeting DNA for different therapies, and they need to identify DNA or small molecules that selectively bind to DNA to turn on or off the gene expression related to a particular disease," said Chad A. Mirkin, George B. Rathmann Professor of Chemistry, professor of medicine and professor of materials science and engineering, who led both studies. "Our method, which is simpler, faster and more convenient than conventional methods, should help researchers zero in on potential anti-cancer agents from their large libraries of candidates more quickly."

In the JACS paper, the researchers demonstrated that when a triplex binder binds to a given DNA triple helix in solution the strength of that binding event can be detected by

Contact: Megan Fellman
Northwestern University

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