In a study published yesterday in Nature Chemistry, a team of Yale University scientists reported a novel approach to glycosylation that they say is simple and works in water at room temperature.
A wide range of biochemical probes and therapeutic agents—everything from antibiotics to Alzheimer's disease biomarkers—rely on the glycosylation process, which is highly specific and can make synthesis of such compounds, for testing or large-scale production, difficult.
"Glycoproteins serve a myriad of functions in biological chemistry," said Scott Miller, the Irénée du Pont Professor of Chemistry at Yale and co-corresponding author of the study. "Synthesis of these compounds is very challenging, and has limited the extent to which people can make multiple variants in order to find the best biochemical probes and therapeutics."
Many glycoprotein molecules are currently made using an enzyme catalyst, according to Alanna Schepartz, Sterling Professor of Chemistry at Yale and the study's other co-corresponding author. The Yale team's approach does not require an enzymatic reaction, allowing the process to be generalized to create large numbers of different compounds.
Another advantage of the new process, the researchers said, is that it occurs in water as the solvent. Often, organic synthesis of bioactive compounds happens in non-aqueous solvents, because water has a tendency to react with many catalysts and chemical agents.
"There is enormous interest right now in strategies to perform selective chemistry on complex biomolecules in water and also in cells," Schepartz said. "This paper lays a strong foundation that we and others can build upon to develop novel and useful chemistry."
Image: Yale University scientists have developed a new approach to glycosylation that works in water.