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 onlinein 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 the naked eye. The color of the solution changes from blue to red when heated, and the temperature at which this occurs indicates the strength of the triplex binder's bond.
Much like tiny bits of gold produce the vibrant red in stained glass windows, the Northwestern team also takes advantage of gold's intense color when the metal is measured on the scale of atoms. The researchers start with gold nanoparticles, each just 13 nanometers in diameter, held together by DNA in a triple helix conformation. Because they are held together within a certain critical distance, the gold nanoparticles -- and the solution they are in -- are blue. When the solution is heated, the DNA breaks apart, and the gold nanoparticles, no longer in close proximity to each other, are now bright red.