# Chemo-enzymatic synthesis of nucleotide sugar libraries and therapy-relevant derivatives

> **NIH NIH R44** · CHEMILY, LLC · 2021 · $341,906

## Abstract

Glycans and glycoconjugates are widespread in nature and play pivotal roles in cell-cell
recognition, cell differentiation, and immunological responses. Most glycans and glycosylation reactions
require nucleotide sugars as their essential building blocks. Therefore, the commercial availability of
nucleotide sugars will determine future opportunities for carbohydrate-based innovations, just as the
availability of nucleotides was a prerequisite for today’s $6.1 billion PCR market of DNA-based
technologies. Due to glycoscience’s reliance on nucleotide sugars, there is an urgent need for a
production pipeline to provide these essential reagents.
 The goal of our “Chemo-enzymatic synthesis of nucleotide sugar libraries and therapy-relevant
derivatives” Fast-Track project is to meet this need and commercialize a stable, affordable and diverse
supply of nucleotide sugars to drive advances in glycoscience. It is our long-term objective to bring 11
nucleotide sugars, 26 nucleotide derivatives, and the associated processes to market. In Phase I Aim 1,
we will enzymatically synthesize GDP-L-Fuc, GDP-Man, CMP-Neu5Ac, CMP-Neu5Gc, and 7 UDP
sugars: Glc, Gal, GlcNAc, GalNAc, GlcA, GalA, and Xyl. In Aim 2, we will create optimized in situ
generation systems for the UDP-, GDP-, and CMP-sugars to be coupled with transferase reactions. Our
methods will utilize de novo or salvage pathway enzymes and be scaled up to 1 gram production
reactions. In Phase II Aim 1, we will chemically modify the nucleotide sugars to form 26 new derivatives
containing azido, fluoride, deoxy or methoxy functional groups at various positions on CMP-Neu5Ac,
GDP-L-Fuc, and UDP-GlcNAc/GalNAc. In Aim 2, we will further optimize all 37 production platforms for
commercialization. Our methods will combine chemical synthesis with de novo and salvage pathway
enzyme reactions to produce the most efficient products.
 The health relevance of this project is linked to developments in glycan technology, due the
fundamental nature of nucleotide sugars as building blocks for glycoconjugates and polysaccharides. A
stable supply of nucleotide sugars and their derivatives will facilitate experiments that advance our
understanding of cell surface markers, cell recognition, and protein-carbohydrate interactions. In turn,
this cell specific information has the potential to impact individualized medicine, drug-delivery, and cell
targeting therapies.

## Key facts

- **NIH application ID:** 10225322
- **Project number:** 5R44GM123880-05
- **Recipient organization:** CHEMILY, LLC
- **Principal Investigator:** Wanyi Guan
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $341,906
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225322

## Citation

> US National Institutes of Health, RePORTER application 10225322, Chemo-enzymatic synthesis of nucleotide sugar libraries and therapy-relevant derivatives (5R44GM123880-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10225322. Licensed CC0.

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