DNA’s hidden power could transform how we make medicines

Many medicines are chiral, meaning they exist in two mirror-image forms -- similar to a pair of hands -- that can behave differently inside the body. One version may effectively treat disease, while the other could have little benefit or even cause harm. Producing only the desired form is a major challenge in drug development, but the new DNA-guided method could make this process cleaner, simpler, and more environmentally sustainable.

DNA and proteins naturally attract one another in living cells because DNA's phosphate groups carry a negative charge, while many amino acids are positively charged. The NUS team, led by Assistant Professor Zhu Ru-Yi from the Department of Chemistry, wondered whether this same type of attraction could help control chemical reactions in the lab. Their goal was to see if DNA could guide molecules to react in specific, predictable ways.

How DNA's Phosphates Guide Chemistry

The researchers found that certain phosphate groups in DNA can pull in positively charged molecules during a chemical reaction, helping them align correctly -- much like a magnet drawing a metal bead into place. This process, known as "ion pairing," keeps the reacting molecules close together and oriented just right to produce a single, desired mirror-image product. The team showed that this guiding effect works across several different chemical reactions.

To pinpoint which phosphates were responsible for this guiding ability, the team created a new experimental approach called "PS scanning." They systematically replaced individual phosphate sites in the DNA with nearly identical substitutes and repeated their tests. When swapping out a phosphate reduced the selectivity of the reaction, it revealed that the original site played a crucial role. To confirm their findings, they collaborated with Professor Zhang Xinglong from The Chinese University of Hong Kong, who used computer simulations to validate the experimental results.

The work was published in Nature Catalysis on October 31, 2025.

DNA as a Green Chemistry Tool

Asst Prof Zhu explained, "Nature never uses DNA phosphates as catalysts, but we have shown that if designed properly, they can act like artificial enzymes."

He added that the discovery could make chemical manufacturing both more sustainable and more efficient, especially when producing complex, high-value pharmaceuticals.

The team plans to continue exploring how DNA phosphates can be used to design and produce chiral (mirror-image) compounds for next-generation drug development.