Slight nuances in the structure of DNA have been previously implicated in breast cancer and other diseases but are extremely difficult to detect—until now. Studying how DNA folds may impact the human body, either positively or negatively, requires scientists to first detect their presence. Chemists at the University of California Riverside have designed a chemical nose that sniffs out bits of DNA folded in unusual ways.
In the study, researchers modified a concept previously used to sense chemical components in unique vintages of wine. To do this, UCR organic chemistry professor Richard Hooley and his colleagues altered the chemicals in the system to detect target molecules by using multiple receptors that interact with DNA folds. The chemical nose comprises three parts: host molecules, fluorescent guest molecules and target DNA. When the desired folds are present, the fluorescent guest glows, alerting scientists to their presence. Researchers discovered they could detect a specific type of G-quadruplex comprising four guanines, whose folds are known to regulate gene expression and play a key role in keeping cells healthy. The study was published in the journal Nature Chemistry.
"Now we think we can do more," said UCR chemistry professor Wenwan Zhong. "There are other 3D structures in DNA, and we want to understand those as well."
To build on their success, researchers will analyze RNA folding to understand its complex structure. RNA is more difficult to analyze but has great potential for disease research. The chemists will also examine how forces that damage DNA affect the way they fold.
Photo: Illustration of the chemical “nose” sensing a G-quadruplex structure. Credit: Richard Hooley/UCR