Chemical with ‘sense of smell’ sniffs out abnormal DNA linked to diseases

RIVERSIDE, Calif. —  Chemists from the University of California, Riverside have developed a chemical with a “keen sense of smell” for abnormally structured DNA molecules. This so-called DNA “sniffer” can find critical changes in our body’s building blocks that could influence the development of certain diseases.

The physical shape of DNA is directly associated with its function. For example, if a section of DNA is overlapping another strand or part of the same strand, that particular section cannot be used to form essential proteins. DNA with structural variations such as this have shown up in conditions such as breast cancer, as well as Alzheimer’s disease. Finding these variations in DNA, however, have proven to be incredibly challenging for scientists.

Wenwan Zhong, a professor of chemistry at the university, says there are both good and bad effects of abnormally structured DNA. “If a DNA sequence is folded, it could prevent the transcription of a gene linked to that particular piece of DNA,” Zhong says in a statement.  “In other words, this could have a positive effect by silencing a gene with the potential to cause cancer or promote tumors.”

However, the downside is that abnormally folded DNA molecules “could potentially keep viral proteins from being produced to minimize immune response,” adds Zhong.

DNA normally looks similar to a twisted ladder, with the nucleotides adenine, thymine, cytosine, and guanine bonded to each other forming the “steps.” Abnormally-shaped DNA molecules tend to overlap in areas with an abundance of guanine. This produces a square-shaped formation referred to as a “G-quadruplex.”

To create the chemical “sniffer” for these molecules, Richard Hooley, a professor of organic chemistry at UCR, and his team designed a network composed of binding sites for the misshapen DNA molecules and components that were stimulated to glow once bonded to the DNA. “Humans detect smells by inhaling air containing odor molecules that bind to multiple receptors inside the nose. Our system is comparable because we have multiple receptors able to interact with the DNA folds we’re looking for,” says Hooley.

Although the experiment was a success, the system was only tested on abnormally-shaped DNA with exactly four molecules of guanine. “Now we think we can do more,” says Zhong. “There are other three-dimensional structures in DNA, and we want to understand those as well.”

For future studies, the team would like to determine how the shape of DNA is impacted by stresses related to DNA alterations. Additionally, since RNA is responsible for directly creating proteins from DNA, the team will investigate the abnormal folding of RNA molecules. “RNA has even more complex structures than DNA and is more difficult to analyze, but understanding its structure has great potential for disease research,” says Zhong.

This research is published in the journal Nature Chemistry.