# Chemoenzymatic synthesis of a human milk oligosaccharide array for discovery of therapeutic leads

> **NIH NIH R43** · VIAMUNE, INC. · 2020 · $150,000

## Abstract

Project Summary / Abstract:
Human milk oligosaccharides (HMOs) are the third largest component of breast milk and have been described
to convey developmental benefits to the newborn. HMOs may comprise a wealth of untapped therapeutic
opportunities as this unique class of molecules can interact with, and thereby potentially modulate, mediators
of inflammation. Unfortunately, investigation into the therapeutic utility of HMOs has been hindered by lack of
access to individual structures in appropriate quantity and purity for thorough biological evaluation and
preclinical development. Current methods for evaluating the biological role of HMOs rely on: 1) probing a
heterogeneous mixture of HMOs bearing similar structural characteristics or 2) attempting to isolate individual
structures from pooled milk using exhaustive chromatography techniques. Neither strategy provides a platform
for readily examining individual HMOs against a panel of biological targets, nor an efficient strategy for target
scale-up required for mode-of-action, structure-activity relationships, and pre-clinical development. There is an
urgent need to develop a synthetic strategy that can access well-defined HMOs for high-throughput screening
and is scalable to provide identified leads in appropriate quantity for biological evaluation and ligand
optimization.
To address the problem of compound availability, a chemoenzymatic synthetic strategy will be employed to
develop a library comprising 100 HMOs. The strategy aims at chemically synthesizing a limited number of
advanced intermediates which can be further modified by a panel of glycosyltransferases to provide a
collection of targets with significant structural diversity. The library will be immobilized on microarray slides for
high-throughput screening and in first instance, will be screened with carbohydrate recognizing proteins
involved in intestinal inflammation. Identified leads will be examined for anti-inflammatory efficacy using an in
vitro dendritic cell model. Finally, a complementary, convergent synthetic approach will be developed to
provide large-scale access to efficacious hits required for in vivo animal studies and preclinical development.
The short-term goal of this proposal is the successful synthesis of the largest collection of synthetic HMOs to
date for assay implementation and early pharmacological screening. Additionally, our convergent synthetic
methodology will provide a means to scale-up any HMO library member in appropriate quantity for preclinical
development. The long-term goal is to use this methodology to facilitate the development of HMOs to address
deficiencies in neonatal and infant formulas as well as investigate potential avenues for development of anti-
inflammatory therapeutics.

## Key facts

- **NIH application ID:** 9876987
- **Project number:** 5R43GM131558-02
- **Recipient organization:** VIAMUNE, INC.
- **Principal Investigator:** Anthony Prudden
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,000
- **Award type:** 5
- **Project period:** 2019-02-19 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876987

## Citation

> US National Institutes of Health, RePORTER application 9876987, Chemoenzymatic synthesis of a human milk oligosaccharide array for discovery of therapeutic leads (5R43GM131558-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9876987. Licensed CC0.

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