Sugars known as glycans form dense layers around cells. Yet, unlike DNA, proteins, and other cellular components, they are often overlooked in biological research because reliable tools to study them are limited.

A new technology developed by University at Buffalo scientists, detailed in a July 18 Nature Communications paper, aims to overcome this challenge.

At the core of the breakthrough is a pig enzyme called ST3Gal1. Normally, this enzyme helps construct glycans. UB researchers, however, reengineered it to recognize and bind to glycans instead of building them. The result is a glycan binding enzyme named sCore2, which enables scientists to study and potentially treat diseases by examining sugar patterns on cell surfaces.

In its natural state, ST3Gal1 plays a key role in glycan synthesis. But when reengineered into sCore2, it becomes a sugar-binding protein that functions like a molecular spotlight, explains study corresponding author Sriram Neelamegham, UB Distinguished Professor in the Department of Chemical and Biological Engineering.

This matters because glycans are notoriously difficult to detect due to their structural complexity and weak immune visibility. Yet, we know they are central to how cells communicate, particularly in disease. This new tool allows us to capture a much more detailed view of glycans, which could transform how we understand, detect, and treat illness.

Neelamegham adds that the strategy converting enzymes from sugar-builders into sugar binders could be extended to other human genes and classes of enzymes.

The study, building on previous work published in Small and reviewed in Glycobiology, brought together UB researchers from biomedical engineering, pathology and anatomical sciences, and medicine.

To create sCore2, the team introduced a mutation known as H302A into ST3Gal1. This modification served two purposes: it disabled the enzyme’s normal sugar-building function while giving it a new ability to target and bind to a specific glycan, sialylated core 2 O glycans.

The researchers refined the enzyme further using mammalian surface display technology, a method that presents proteins on the surface of mammalian cells, enhancing its glycan binding performance. They then fused sCore2 to a fluorescent antibody that glows under certain light conditions, allowing them to track sugar patterns in human blood and tissue cells.

Tests revealed that sialylated core-2 O-glycans are more abundant in mature immune cells and certain cancer tissues, particularly breast cancer. The tool also uncovered previously unknown sugar signatures in organs such as the spleen and pancreas.

These findings suggest that sialylated core-2 O-glycans could serve as valuable biomarkers for cancer detection, immune cell changes, and other disease processes. The work also lays the foundation for developing tailored sugar binding proteins and building a library of such tools for diagnostic and therapeutic use.

The results are very promising,  Neelamegham says, noting that the team is already pursuing follow up studies.

The researchers have filed a provisional patent covering sCore2’s composition and methods for creating it. The project received support from the National Institutes of Health and continues with funding from UB’s New York State Center of Excellence in Bioinformatics and Life Sciences, an economic development initiative backed by NYSTAR.

Source: https://www.buffalo.edu/research/events-announcements.host.html/content/shared/university/news/ub-reporter-articles/stories/2025/08/neelamegham-enzyme.detail.html