DNA's Phosphate Groups: A Breakthrough in Drug Development

Researchers at the National University of Singapore have made a significant discovery regarding the role of DNA in drug development. They found that specific regions of DNA, particularly the phosphate groups, can act like tiny hands that guide chemical reactions, facilitating the production of chiral compounds.

Chiral compounds exist in two mirror-image forms, which can have vastly different effects in the body. This ability to produce only the desired form of a drug is crucial, as one version may treat a disease effectively while the other may be ineffective or even harmful.

The NUS team, led by Assistant Professor Zhu Ru-Yi, explored how DNA's negative charge, due to its phosphate groups, attracts positively charged molecules. This attraction helps align the molecules during a chemical reaction, allowing them to bond in a specific orientation.

This process, known as ion pairing, effectively keeps the reacting molecules close together, producing the desired mirror-image product. The researchers tested this guiding effect across several different chemical reactions.

To identify which phosphate groups were responsible for this phenomenon, they developed a novel approach termed PS scanning, systematically replacing individual phosphate sites in the DNA with substitutes.

The results showed that swapping out certain phosphates reduced the selectivity of the reactions, indicating their crucial role in directing the process. Their findings were supported by computer simulations from Professor Zhang Xinglong at The Chinese University of Hong Kong, confirming the experimental results.

This breakthrough suggests that DNA phosphates, although not typically used as catalysts in nature, can be engineered to function as artificial enzymes. Asst Prof Zhu emphasized that this could lead to greener and more efficient chemical manufacturing processes, especially for the production of complex pharmaceuticals.

The research team plans to further investigate the potential of DNA phosphates in designing and producing chiral compounds, thereby advancing drug development. The findings were published in Nature Catalysis on October thirty-first, twenty twenty-five, highlighting a promising new avenue for the pharmaceutical industry.