Scientists try to simplify the process of in-lab glycosylation by borrowing nature's formula for sugar synthesis.

Nutritionists are not the only ones who avoid sugars. Synthetic chemists do that too. While nature is able to shift one sugar molecule to another chemical seamlessly, scientists often struggle to replicate the same procedure in their labs, also known as glycosylation, which is important to develop vaccines and pharmaceutical products.

Seeking Guidance From Nature

"The biological universe is coated with sugars," said Samuel M. Levi and Qiuhan Li, graduate students in Harvard University's Department of Chemistry and Chemical Biology. "Cells, bacteria, viruses and other organisms use sugars as a means of communication, recognition, and even defense." The researchers explain that nature practically lives on sugars.

Levi and Li further explain that even though there are several techniques to perform chemical glycosylation, they are mainly used by carbohydrate chemistry experts. However, the scientists are now working toward extending this expertise to non-experts by taking help from nature.

Revealing Nature's Secret Ingredient

Nature conducts sugar synthesis on its own with the help of phosphates, but to replicate this process in the lab, synthetic chemists use materials such as halides and sulfinates rather than phosphates. So while the phosphates used by nature may not be that fast in reacting, they are definitely more stable than its lab alternative. In fact, the enzymes responsible for triggering the reaction are able to identify phosphate monomers that expedite the reaction.

However, until now, the researchers have to use an external catalyst in the form of heat or energy to accelerate a slow-reacting phosphate, but outside the lab, it is able to do so without the volatile temperatures or excessive heat.

Now, a paper published in the Proceedings of the National Academy of Sciences led by Eric Jacobsen, professor of chemistry and chemical biology, along with Levi, Li, and Andreas R. Rötheli, have discovered the nature's secret — a "precisely designed hydrogen-bond-donor catalyst."

The researchers found that with this catalyst, the bond between phosphate and chloride is 19 times stronger, which is also another common ingredient required for the reaction. Additionally, it is able to bind sugars to drug molecules, natural products, and amino acids in user-friendly conditions. Levi and Li explain that through this method, they are able to give phosphate just enough push to get started, but not without its own set of limitations.