Chemists design a faster production process for essential sugars

The cells of all living organisms are covered with a dense layer of very complex carbohydrates. These carbohydrates, also known as glycans, are essential mediators of a wide range of biological and pathological processes. In order to study the glycans in detail, scientists had to carry out a production process involving more than 100 chemical steps, but researchers at the University of Utrecht have recently developed a much-improved process. faster and more efficient. The researchers published their results in Nature Chemistry.

Trunk and branches

Glycans play a key role in many biological and pathological processes, ranging from embryogenesis to immune regulation, through the inhibition of inflammation and cancer. Glycans can be used as biomarkers to identify cancer cells, but they are also essential components of most biomolecule-based pharmaceuticals.

Glycans are however much more complex than DNA or proteins: they consist of a trunk with two to four asymmetric branches, and the more branches they have, the more complicated they are to synthesize. In fact, it often takes up to 100 chemical steps to produce glycans in the laboratory.

Geert-Jan Boons and Gerlof Bosman, researchers at the University of Utrecht, are trying to remedy this situation in close collaboration with their colleagues at the University of Georgia in the United States. "We are taking control of glycans biosynthesis," says Boons. Researchers have developed a method from a glycopeptide that can be readily obtained from egg yolk powder as a constituent of the production of glycans.

Size to grow

The first step of the new production process is to "cut" the glycopeptide, until only the trunk and the branching points remain. Researchers can individually activate or deactivate each branch point, allowing them to push the branches one by one by unlocking them individually, then administering enzymes that can create specific branches. This allows the researchers to attach the asymmetric branches of the glycan to the trunk in a controlled manner.

Ten steps

Using this new method, the researchers were able to dramatically reduce the production process to just ten steps. Boons explains: "We used the glycopeptide to produce the glycosyl-asparagine substance, a sugar-containing amino acid." We then subjected the glycosyl asparagine to five chemical and enzymatic steps, giving a two-branched compound. This first We then used recombinant enzymes to produce a four-branched glycosyl-asparagine in just five additional steps, at the base of producing a wide range of N-glycans that play a role in many diseases. such as cancer and viral infections can also be used for the production of biopharmaceuticals.