# Synthesis and Function of Antibody Fc Domain Glycoforms

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $301,550

## Abstract

Project Summary/Abstract
Antibodies are an important class of glycoproteins. Compelling experimental data have shown
that the fine structures of the highly conserved Fc glycans in IgG type antibodies can have
profound effects on the antibody’s biological functions and, in the case of therapeutic antibodies,
the clinical efficacy, such as antibody-dependent cellular cytotoxicity (ADCC), complement-
dependent cytotoxicity (CDC), activation of apoptosis, and anti-inflammatory activities. More
recently, it was reported that a single oligomannose type glycan at the IgE-Fc domain was
responsible for high-affinity binding to IgE receptor on mast cells and was critical for initiation of
allergic reactions. However, progress in understanding the functional roles of antibody
glycosylation is hampered by the tremendous structural heterogeneity of Fc glycosylation.
Gnetic approach to glycoengineering has achieved some successes but the antibody
glycoforms that can be generated by genetic approach are limited. Currently there is no general
method avaiable to control glycosylation to a pre-defined homogeneous form during
recombinant antibody production. In this application, we propose to explore a chemoenzymatic
method that we recently developed to make various homogeneous IgG and IgE glycoforms.
Through performing Fc receptor binding studies, we aim to understand how different glycan
structures modulate the effector functions of IgG and IgE and to apply the knowledge obtained
for developng better therapeutics. Three specific aims are proposed to achieve the goal. Aim 1
is to further explore the chemoenzymatic method for antibody glycoengineering by investigating
enzyme structures, searching for new enzymes and mutants, and evaluating new glycan
substrates. Aim 2 is to establish a general site-specific conjugation method for constructing
homogeneous antibody-drug conjugates. Functional tags will be introduced to Fc glycan site-
specifically and a toxin will be chemoselectively ligated to the Fc glycan to provide
homogeneous ADCs. Aim 3 is to perform site-specific glycosylation remodeling of IgE Fc for
probing the glycosylation functions in allergic reactions. A successful pursuit of the proposed
research could lead to the creation of new IgG and IgE glycoforms with novel biological
properties. The chemoenzymatic method may become a general platform technology for site-
specific antibody-drug conjugation and labeling. The study on IgE Fc glycosylation, if
successful, will fill a gap of our knowledge in glyco-immunology related to allergic reactions and
diseases.

## Key facts

- **NIH application ID:** 9841400
- **Project number:** 5R01GM096973-09
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** LAI-XI WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $301,550
- **Award type:** 5
- **Project period:** 2011-07-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841400

## Citation

> US National Institutes of Health, RePORTER application 9841400, Synthesis and Function of Antibody Fc Domain Glycoforms (5R01GM096973-09). Retrieved via AI Analytics 2026-07-01 from https://api.ai-analytics.org/grant/nih/9841400. Licensed CC0.

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