Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

29.03.2006
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 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.

When a triplex binder binds to DNA it creates a stronger bond that requires a higher temperature to break apart the DNA strands. By adding different triplex binders to a solution with a specific DNA sequence between the gold nanoparticles, the colorimetric method can distinguish molecules that are strong binders, medium binders and weak binders. (Current methods using fluorescence can only indicate whether or not a bond has formed.) When heated, the solution with a triplex binder that is a weak binder turns red at a lower temperature than the solution with a strong binder. This color change from blue to red allows the researchers by simple visual inspection to see which triplex binders bind to the DNA and how strongly they bind.

"It’s impossible to do a full-blown study on every triplex binder or small molecule," said Mirkin, who is director of Northwestern’s Center for Cancer Nanotechnology Excellence. "You need to narrow down the possible candidates. This method allows researchers to identify the types of triplex binders or molecules that are effective for a given DNA sequence. Most diseases have a unique genetic code associated with them, and by manipulating the genes with the right triplex binders or small molecules you can develop new therapies."

A certain DNA sequence might be linked to colon cancer, for example, and the proteins expressed by that DNA produce cancer cells. By identifying a triplex binder or small molecule that binds effectively to that particular DNA sequence, a drug can be developed that shuts down protein production and stops cancer cells from proliferating.

Their next step, said Mirkin, is to challenge the research community to provide libraries of triplex binders and small molecules for his research teams to test. Any interaction with DNA, whether it be with small molecules, proteins or other DNA, can be identified by the colorimetric method. "We want to identify the real winners," said Mirkin.

In addition to Mirkin, other authors on the JACS paper are post-doctoral fellow Min Su Han (first author) and graduate student Abigail K. R. Lytton-Jean, both from Northwestern University.

Megan Fellman | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>