# Chemoenzymatic glycan editing for deciphering biological functions of glycans

> **NIH NIH R35** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $146,126

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cell-surface glycans participate in numerous biological processes, including signal transduction, cell-cell
communication and development. Aberrant glycosylation is a hallmark of human disease. At a molecular level,
glycans represent the first points of contact between cells. However, not directly encoded in the genome, these
biomolecules are challenging to study using molecular biology techniques alone. Metabolic oligosaccharide
engineering (MOE) developed in late 1990’s has revolutionized the way for the labeling and visualization of
glycans in living organisms. In this method, cells’ own glycan biosynthetic machinery is hijacked to incorporate
unnatural monosaccharides with linkage promiscuity.
 Complementary to MOE, chemoenzymatic glycan editing has emerged as a valuable tool to probe and
modify glycan structures within a cellular environment. Unlike MOE, chemoenzymatic glycan modification
utilizes recombinant glycosyltransferases to transfer natural or unnatural monosaccharides with novel functions
from activated nucleotide sugars to glycoconjugates on the cell surface with linkage specificity. For these
reasons, chemoenzymatic glycan modification provides a facile and more precise way for probing the function
of glycans in their native environments.
 Building upon our successful application of chemoenzymatic glycan editing, in the next five years we will
expand our chemoenzymatic tool kits to study glycans’ cellular functions with a focus on the special roles of N-
acetyllactosamine (LacNAc), fucose and sialic acid in immune regulation. Cell-surface LacNAc mediates
ligand-receptor binding and sets a threshold for initiating the downstream signaling for immune cell activation.
LacNAc residues are dynamically modified by sialic acid and/or fucose. However, the specific roles of these
modifications in immune regulation and disease progression remain obscure.
 We are particularly interested in finding out: (1) if changes in LacNAc and fucosylation status can serve
as glycan signatures of T cell exhaustion during which T cells gradually lose their cytokine production,
proliferation and cytotoxic capacity; (2) Can cell-surface in situ LacNAc fucosylation be used to boost the
efficacy of antitumor immunity of T cells and NK cells? In parallel, we will develop chemoenzymatic tools for
profiling sialylated glycoprotein ligands of Siglecs (sialic acid-binding immunoglobulin-type lectins) and for the
identification of unnatural, high-affinity and specific ligands to interrogate Siglec functions.
 Through these studies, we will gain a deeper understanding of how LacNAc, fucose and sialic acid are
involved in the regulation of the immune cell activation, effector function and exhaustion. Tools developed in
this project can also be used to study other types of glycans and their interactions with glycan binding proteins.

## Key facts

- **NIH application ID:** 10799053
- **Project number:** 3R35GM139643-03S1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Peng Wu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $146,126
- **Award type:** 3
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799053

## Citation

> US National Institutes of Health, RePORTER application 10799053, Chemoenzymatic glycan editing for deciphering biological functions of glycans (3R35GM139643-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10799053. Licensed CC0.

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