Scientists reengineer enzyme to study diseases via sugar patterns on the surface of cells
Lisa Lock
scientific editor
Robert Egan
associate editor
Sugars known as glycans form dense envelopes around cells. But they're often ignored in biological investigations because, unlike DNA, proteins and other cellular components, tools to study them are lacking. A new technology, presented by University at Buffalo scientists in a study in Nature Communications, aims to break this barrier.
The tool centers on a pig enzyme called ST3Gal1, and how scientists retrained it to bind to glycans instead of building them. This new glycan-binding enzyme, which scientists named sCore2, could help analyze and treat diseases via sugar patterns found on the surface of cells.
"In its natural state, ST3Gal1 plays a key role in building glycans. But after we reengineer it as sCore2, it becomes a sugar-binding protein that acts like a molecular spotlight," says the study's corresponding author Sriram Neelamegham, Ph.D., UB Distinguished Professor in the Department of Chemical and Biological Engineering.
"This is important," he says, "because glycans are difficult to detect due to their structural complexity and the fact that they do not provoke strong immune responses. But we know that glycans play a key role in how cells communicate, especially during disease. And ultimately, this new tool gives us a much more nuanced view of glycans which could improve how we understand, detect and treat disease."
He adds, "This approach—switching the function of enzymes from sugar building to sugar binding—can be extended to other genes in humans and also other classes of enzymes."
The work, which builds upon a published in Small and a in Glycobiology, was performed by UB faculty from the Department of Biomedical Engineering, the Department of Pathology and Anatomical Sciences, and the Department of Medicine.
To make sCore2, scientists began by introducing a mutation called H302A to ST3Gal1.
This alteration served two purposes. First, it disabled ST3Gal1's main enzymatic function, which is to help build complex chains of sugars. Secondly, it gave the modified ST3Gal1 a new role: to seek out and bind to one type of glycan known as sialylated core-2 O-glycans.
The scientists made additional refinements—including using mammalian surface-display technology, which is a method used to express proteins on the surface of mammalian cells—that improved sCore2's glycan-binding capabilities.
They then attached sCore2 to a fluorescent antibody that glows under certain lighting conditions. Researchers tested the tool on human blood and tissue cells.
They found that sialylated core-2 O-glycans were more common on mature immune cells and some cancerous tissues, especially breast cancer. The tool also spotlighted previously unknown sugar patterns in the spleen, pancreas and other organs.
The work suggests that sialylated core-2 O-glycans could serve as a biomarker for cancer detection, immune cell changes, and other disease states. It also lays the groundwork for creating more customized sugar-recognizing proteins, and the potential to create a library of such tools that can be used to diagnose and treat disease.
"The results are incredibly promising," says Neelamegham, noting the team is already engaged in follow-up work.
Researchers have filed a provisional patent application that relates to sCore2's composition, as well as the methods to create it.
More information: Ryoma Hombu et al, Engineering glycosyltransferases into glycan binding proteins using a mammalian surface display platform, Nature Communications (2025).
Journal information: Small , Nature Communications
Provided by University at Buffalo
